Tag Archive for: genetic testing

Tools for Accessing Personalized Advanced Prostate Cancer Treatment and Care

Tools for Accessing Personalized Advanced Prostate Cancer Treatment and Care from Patient Empowerment Network on Vimeo.

What steps can advanced prostate cancer patients take to help them access the most personalized treatment approach for their disease? This animated video reviews key treatment decision factors, how biomarker testing results affect care, and advice for self-advocacy. 

See More From INSIST! Prostate Cancer

Related Resources

What Questions Should Prostate Cancer Patients Ask About Testing and Test Results

What Questions Should Prostate Cancer Patients Ask About Testing and Test Results? 

How Do Biomarker Test Results Impact Prostate Cancer Treatment Options

How Do Biomarker Test Results Impact Prostate Cancer Treatment Options

Essential Testing Following a Prostate Cancer Diagnosis

Essential Testing Following a Prostate Cancer Diagnosis 


Transcript:

Every advanced prostate cancer patient is unique AND so is their disease. Advances in research are making personalized medicine a reality, tailoring care and therapy choices based on the genetic makeup and individual characteristics of a patient’s disease.   

As prostate cancer research evolves and treatment options expand, it’s vital that patients work with their healthcare team to find the best treatment approach to treat their specific cancer.  

An essential step to accessing personalized medicine is biomarker testing, which identifies key markers such as genes, proteins, or other molecules in a sample of tissue, blood, or other bodily fluid. The results of these tests can provide a fuller picture of the prostate cancer’s type, stage, and aggressiveness and may help predict how the cancer will behave. 

The test results can also identify which treatment approach may be most effective, through the presence of certain molecular markers.  For example, if a tumor has either high microsatellite instability (MSI high) or mismatch repair defects (dMMR), a prostate cancer patient may benefit from immunotherapy. Or a PARP inhibitor therapy may be more effective if the presence of mutations in certain DNA damage repair genes is detected. 

In addition to biomarker test results, other factors that physicians consider when recommending a treatment approach include:  

  • A patient’s age, overall health, and any pre-existing conditions. 
  • The type, stage, and grade of prostate cancer. 
  • And, potential side effects or impact on their lifestyle. 
  • And, the patient’s preference. 

Along with these considerations, it’s vital that patients discuss the benefits and drawbacks of each option with their team. So, how can you be proactive in order to access personalized care? 

  • Ensure that your doctor has experience treating prostate cancer. Consider consulting a specialist or obtaining a second opinion, so you can feel confident in your diagnosis and treatment plan. 
  • Ask a friend or loved to join you during key discussions with your provider, to help you process the information and to make decisions. 
  • And, be sure to request all essential testing, including biomarker testing, and ask how the results may affect your prognosis and treatment options.  
  • Discuss ALL of the treatments available to you, including any potential side effects.  
  • And ask if there is a clinical trial that could be right for you.
  • Finally, and most importantly, YOU should be at the center of your prostate cancer care. Share your opinions and ask questions throughout the process, so you feel empowered and informed. 

To learn more about prostate cancer and to access tools for self-advocacy, visit powerfulpatients.org/PC. 

Newly Diagnosed With Follicular Lymphoma? Start Here

Newly Diagnosed with Follicular Lymphoma? Start Here from Patient Empowerment Network on Vimeo.

How are follicular lymphoma treatment options commonly explained to patients? Expert Dr. Sameh Gaballa shares how he walks patients through treatment options, POD24 and FLIPI tests that help guide treatment options, and follicular lymphoma staging.

Dr. Sameh Gaballa is a hematologist/oncologist specializing in treating lymphoid malignancies from Moffitt Cancer Center. Learn more about Dr. Gaballa.

See More from START HERE Follicular Lymphoma

Related Resources:

What Exactly is Follicular Lymphoma? An Expert Explains

What Exactly is Follicular Lymphoma? An Expert Explains

Follicular Lymphoma Patient Expert Q&A: Start Here

Follicular Lymphoma Patient Expert Q&A: Start Here

What Follicular Lymphoma Treatments Are Available?


Transcript:

Lisa Hatfield:

So, Dr. Gaballa, let’s start here. How do you explain follicular lymphoma treatment options and prognosis to your newly diagnosed patients? And what does shared decision-making look like in your office?

Dr. Sameh Gaballa:

Oh, absolutely. So follicular lymphoma, you really have to explain to the patient what, how are we coming to the recommendation that we’re currently giving. So if we think this is, this patient is a good candidate for a watch-and-wait approach, for example, we really have to walk them through why that really is the best option and not why should we jump on treatments and vice versa, if we think this patient needs to be treated, how do we really…the patient really has to understand all the other treatment options and why this needs to be treated. Because a lot of patients initially, sometimes when you present them with a watch-and-wait approach, if they don’t know all the background, they might not feel very comfortable because they might think, “Well, I have this cancer in me, and we’re not doing anything about it, and that doesn’t really sound too…something I should be doing.”

But then when you explain to them, “Well, you see, you don’t have a lot of disease, those studies have already been done in the past where patients who were treated or not treated, the survival was the same, so there, you might get side effects from the treatment, but not necessarily have benefits. And in the future, should this need to be treated, we have a lot of things to do.” So, really, so this is kind of the shared decision portion where you just have to walk the patients through why that will be the best situation. There is data with single-agent rituximab (Rituxan), even in patients who are asymptomatic, and we have the UK data, and that’s an option.

And that is also offered to some of the patients, even if they’re not symptomatic and they don’t have a lot of disease, if that’s what really the patient wants, if they’re not really comfortable with a watch and wait. And there’s again some data to help justify that. Again, there’s no advantage in overall survival, but sometimes the patients would kind of feel more in control. They feel like, “Okay, I did something about it.” So that’s the shared approach.

In terms of your other question about prognosis, unfortunately that’s an area of an unmet need. I mean, we have some tools to help us differentiate follicular lymphoma patients from each other, which patient is high-risk, meaning those are the patients who might relapse quickly, or they might not respond well to treatments. Unfortunately, we don’t have great tools. We have something called a FLIPI score, which is, we use a number of parameters including clinical parameters like stage or age and some other parameters as well, and we have a scoring system. But it doesn’t 100 percent predict if this is going to be a high-risk follicular lymphoma or a low-risk.

Unfortunately, the best predictor of prognosis for follicular lymphoma, you would know about retrospectively, it’s something called POD24, progression of disease in 24 months. Meaning that if you have a patient who’s treated with chemotherapy and immune therapy, and then they go into remission, and then they relapse again in less than 24 months, progression of disease within 24 months, those are the, those represent about 20 percent of follicular   lymphoma patients, and those represent a high-risk group of patients. That’s the best tool that we have. But unfortunately, if you’re diagnosed today, you’re not going to know if you’re in this group or not until you actually need to be treated and not just treated with immune therapy.

It has to be with chemotherapy as well. And then if you relapse within two years, then we know that this is a high-risk entity. There is genetic testing, there is something called a FLIPI-m7 scoring system. But again, these tools are not great to tease out the low risk from the high-risk follicular lymphoma patients. But 80 percent of patients who are not going to be POD24, meaning that they get treated, they’re in remission for two years or more, and actually those patients have very similar survival to the general population. So, yeah, so a lot of times we don’t know right away, but we do have some tools to kind of give us an idea.

Lisa Hatfield:

Great. Thank you for that information. It’s kind of hard for cancer patients to only know what their prognosis is retrospectively, but that’s a great explanation. Thank you. Okay, another patient question, “How does the staging of follicular lymphoma impact treatment choices?”

Dr. Sameh Gaballa:

Yeah, so as you saw, I didn’t really stress too much about staging, because it’s a blood disease. So the vast majority of patients are going to be what we call stage III to IV disease. So, obviously when you see a patient if if they, they might think that, “Oh my God, I have a stage III to IV cancer,” because that’s really what they’re familiar with. But follicular lymphoma is a blood disease, so by default it’s going to be in a lot of lymph nodes, it might be in the bone marrow as well, but stage III to IV disease follicular lymphoma doesn’t, that does not mean that this is a terminal cancer. Patients could live completely in normal life, even with a stage III to IV follicular lymphoma. This is not like a breast cancer or colon cancer where stage is everything.

But why do we have a staging system? Obviously, there’s a need to have staging system for all cancers, but clinically, the only time it makes a difference is there’s a small group of patients who have a truly stage I or II disease, meaning just one group of lymph nodes on one side of the diaphragm that may fit within one radiation field. So if you have someone who’s just coming in with one or a few groups of lymph nodes all in one place, we call that a stage I or II follicular lymphoma, not common, because again, most patients are stage III to IV. The only difference there is you can potentially offer those patients radiation therapy if it’s truly localized, but then you would need to do a bone marrow biopsy and confirm that it’s not in the bone marrow.

And if it is localized within one radiation field, that can be offered and we can sometimes give after radiation therapy, either observe it or consider giving rituximab afterwards. But that’s the only time where we’re going to mention staging, again, uncommon because most, the vast majority of patients are going to be stage III to IV. So why would we do that? Why would we irradiate if it’s only one group of lymph nodes? Because there’s about, I mean, if you irradiated, those lymph nodes will go away, but there’s about maybe a, it’s different. The number is different between studies, but about maybe a third of patients, if you irradiate that group of lymph nodes or one lymph node, it actually might not come again in the future. So you might have very long remissions/possible cure if you…and this is the only situation where we would consider treating someone who does not have symptoms, because you could have very long remissions with radiation. 


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Thriving With AML | Advice for Setting Goals and Making Treatment Decisions

Thriving With AML | Advice for Setting Goals and Making Treatment Decisions from Patient Empowerment Network on Vimeo.

When facing an acute myeloid leukemia (AML) diagnosis, treatment decisions may feel overwhelming. AML specialist Dr. Alice Mims shares expert guidance for setting treatment goals with your team, advice for making care decisions, and explains how tests results may impact choices.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims.

See More from Thrive AML

Related Resources:

Phases of AML Therapy | Understanding Treatment Options

Expert Advice | Managing AML Symptoms and Treatment Side Effects

Stem Cell Transplant for AML | What Patients Should Know


Transcript:

Katherine Banwell:

One part of thriving with AML is finding a treatment approach that manages your disease and fits with your lifestyle. Before we talk about therapy, can you tell us how treatment goals are established for an individual patient? 

Dr. Alice Mims:

Sure. So, for individual patients, I think it’s very important that there is an initial discussion that doesn’t feel too shortened that you can have time with your care team to really go into depth about the diagnosis, about the specifics of your particular subtype of acute myeloid leukemia, understanding the treatment options, and then being given time allowed to reflect on all of that information. So, then you can come back and have your questions better answered that may come from that initial discussion. 

And then help you with your team make a decision based on that information that works best for you.  

Katherine Banwell:

Outside of patient preference, what other factors do you take into account when working with a patient to decide on a treatment plan? 

Dr. Alice Mims:

Sure. So, there are multiple different factors that we try to take into account. Again, yeah, most importantly what patients’ goals are like you mentioned, but those include overall health, including different comorbidities, so what other healthcare diagnoses, medications are you taking, what are the patients’ age, thinking about that for long-term goals, overall support from loved ones, family to — just because care can be really involved. And then in particular, thinking about specific features of that individual patient’s AML, including molecular, genetic features of the leukemia. 

Katherine Banwell:

Well, let’s talk more in depth about the test results you just mentioned. 

What is the test for genetic markers? And how is it conducted? 

Dr. Alice Mims:

So, there are a few different tests that we use under that scope of genetic markers. So, those include looking at chromosomal abnormalities of the DNA. So, with cytogenetics, and then also more specific prose where we call FISH testing. And then also we look for specific gene mutations through next-generation sequencing, or PCR testing. And so, we use all of those results together to give us the most information we can about that individual’s leukemia. 

Katherine Banwell:

How has molecular testing revolutionized AML care? 

Dr. Alice Mims:

Oh gracious. It’s really done such – so much for leukemia. And just things are so different even where they were five years ago because of having molecular mutations, that information available. 

So, it helps with discussing prognosis. So, we know that different molecular features can tell us about curative intent and what are the treatment steps we would need to take to give the best chance long-term. And then also now, we’ve evolved to where we have directed therapies that can target mutations or the proteins that arise from those mutations with therapeutic options. 

Katherine Banwell:

Is this testing standard following an AML diagnosis? 

Dr. Alice Mims:

It is standard following an AML diagnosis. That’s recommended within all of the guidelines with patients and really should be done for all patients at initial diagnosis. 

Katherine Banwell:

Can genetic markers or mutations change over time? For example, if a patient relapses, should molecular testing be done again? 

Dr. Alice Mims:

Yes, absolutely. Mutations can evolve. It’s something we call clonal evolution of the leukemia. 

And so you can have mutations that could be present at diagnosis that may no longer be present. Or the opposite can occur where you have new mutations that can appear. And that can lead to different options for treatment. So, it’s very important to retest at time of relapse.  

Katherine Banwell:

What advice do you have for patients who want to ensure that they’ve actually undergone molecular testing? What questions should they be asking their healthcare team? 

Dr. Alice Mims:

I think it’s definitely important to bring this up with the healthcare team. And it should be something at diagnosis and relapse to ask, what are the cytogenetics, what do they look like now, what do the gene mutations, and really as mentioned before, it’s so crucial in talking about prognosis, talking about treatment options that if it doesn’t come up, it’s really something that you should take a pause and try to go back to readdress with your team.  

PODCAST: Managing Life With AML | What You Should Know About Care and Treatment

 

What do you need to know when it comes to managing life with acute myeloid leukemia (AML)? In this webinar, Dr. Alice Mims, an AML specialist and researcher, discusses how treatment decisions are made and how test results may impact therapy. Dr. Mims will shares the latest advances in research and key advice for living well with AML.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims.

Download Resource Guide

See More from Thrive AML


Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for today. Today’s program is a continuation of our Thrive series. And we’re going to discuss navigating life with AML, and how you can engage in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, joining us today is Dr. Alice Mims.  

Dr. Mims, welcome. Would you please introduce yourself? 

Dr. Alice Mims:

Yeah, sure. Thank you, Katherine. I’m Alice Mims. I’m a physician and associate professor at Ohio State University. And also, the section head for the myeloid and acute leukemia program within our division of hematology. 

Katherine Banwell:

Thank you so much for taking the time to join us today, Dr. Mims. We start all of our webinars in our thrive series with the same question; in your experience, what does it mean to thrive with AML? 

Dr. Alice Mims:

Sure, I think that’s a great question. So, really for me, I think thriving with AML is very patient- or person-dependent. It really depends on making sure that your treatment goals align with your care. And so that means really being an active participant in your diagnosis, understanding the disease process, and making sure that your care team really understands what your overall goals are for your treatment. 

Katherine Banwell:

Thank you for that because it helps us to understand as we move through the program today. One part of thriving with AML is finding a treatment approach that manages your disease and fits with your lifestyle. Before we talk about therapy, can you tell us how treatment goals are established for an individual patient? 

Dr. Alice Mims:

Sure. So, for individual patients I think it’s very important that there is an initial discussion that doesn’t feel too shortened that you can have time with your care team to really go into depth about the diagnosis, about the specifics of your particular subtype of acute myeloid leukemia, understanding the treatment options, and then being given time allowed to reflect on all of that information. So, then you can come back and have your questions better answered that may come from that initial discussion. 

And then help you with your team make a decision based on that information that works best for you. 

Katherine Banwell:

Outside of patient preference, what other factors do you take into account when working with a patient to decide on a treatment plan?  

Dr. Alice Mims:

Sure. So, there are multiple different factors that we try to take into account. Again, yeah most importantly what patients’ goals are like you mentioned, but those include overall health, including different comorbidities, so what other healthcare diagnoses, medications are you taking, what are the patient’s age, thinking about that for long-term goals, overall support from loved ones, family to — just because care can be really involved. And then in particular, thinking about specific features of that individual patient’s AML, including molecular, genetic features of the leukemia. 

Katherine Banwell:

Well, let’s talk more in depth about the test results you just mentioned. 

What is the test for genetic markers? And how is it conducted? 

Dr. Alice Mims:

So, there are a few different tests that we use under that scope of genetic markers. So, those include looking at chromosomal abnormalities of the DNA. So, with cytogenetics, and then also more specific prose where we call FISH testing. And then also we look for specific gene mutations through next generation sequencing, or PCR testing. And so, we use all of those results together to give us the most information we can about that individual’s leukemia. 

Katherine Banwell:

How has molecular testing revolutionized AML care?  

Dr. Alice Mims:

Oh gracious. It’s really done such – so much for leukemia. And just things are so different even where they were five years ago because of having molecular mutations, that information available. 

So, it helps with discussing prognosis. So, we know that different molecular features can tell us about curative intent and what are the treatment steps we would need to take to give the best chance long-term. And then also now, we’ve evolved to where we have directed therapies that can target mutations or the proteins that arise from those mutations with therapeutic options. 

Katherine Banwell:

Is this testing standard following an AML diagnosis? 

Dr. Alice Mims:

It is standard following an AML diagnosis. That’s recommended within all of the guidelines with patients and really should be done for all patients at initial diagnosis. 

Katherine Banwell:

Can genetic markers or mutations change over time? For example, if a patient relapses, should molecular testing be done again? 

Dr. Alice Mims:

Yes, absolutely. Mutations can evolve. It’s something we call clonal evolution of the leukemia. 

And so you can have mutations that could be present at diagnosis that may no longer be present. Or the opposite can occur where you have new mutations that can appear. And that can lead to different options for treatment. So, it’s very important to retest at time of relapse. 

Katherine Banwell:

What advice do you have for patients who want to ensure that they’ve actually undergone molecular testing? What questions should they be asking their healthcare team? 

Dr. Alice Mims:

I think it’s definitely important to bring this up with the healthcare team. And it should be something at diagnosis and relapse to ask, what are the cytogenetics, what do they look like now, what do the gene mutations, and really as mentioned before, it’s so crucial in talking about prognosis, talking about treatment options that if it doesn’t come up, it’s really something that you should take a pause and try to go back to readdress with your team. 

Katherine Banwell:

I’d like to move on to treatment now, Dr. Mims. And, of course, treatment takes place in phases for AML. The first is induction therapy. Can you start by defining induction therapy for our audience? 

Dr. Alice Mims:

Sure. So, induction therapy is really terminology that we use to talk about initial therapy for someone with a new diagnosis. So, we can have intensive induction therapies, and non-intensive induction therapies. But the goal for either of those types of treatment is to get the leukemia into remission. 

So, to talk about that in a little bit more detail, for intensive induction regimens, those typically involve cytotoxic chemotherapy. So, you may hear terminology like, “7 + 3 induction,” or “high-dose cytarabine regimens,” but those are typically more intensive regimens that we use that can have increased side effects but may be very important based off the type of acute leukemia. 

And then for non-intensive based regimens, one of the standards has really evolved to be venetoclax (Venclexta) and azacitidine (Vidaza) as a non-intensive regimen that can work very well for a majority of patients. And there are some off shoots of that as well. 

Katherine Banwell:

Okay. And when does stem cell transplant come into play? 

Dr. Alice Mims:

Sure. So, stem cell transplant is something that we all think about at the beginning for anyone with a new diagnosis of acute myeloid leukemia where as we’re working to get back genomic information about the individual’s acute leukemia, we may go ahead and start looking for different donors, doing typing, just in case that’s something that we need as far as someone’s therapy. 

But typically we reserve stem cell transplant for patients who have either intermediate or high-risk features of their AML. Or who may have even favorable respite are not responding as well as we would like when looking at the depth of remission. And so, we always want  to be prepared in case that’s something we need to move forward with as part of their care, if the goal of their treatment is for curative intent. 

Katherine Banwell:

Let’s talk about what happens after the initial phase of treatment. What’s the purpose of consolidation therapy? 

Dr. Alice Mims:

Sure. So, there are a few different purposes we can use consolidation therapy for. So, for patients – consolidation therapy is used for patients who have achieved remission. And then it’s either to try to hopefully get them cure of their AML. The patients have more favorable risk features of their AML and cure is an option through just chemotherapy alone. 

Or it can be used to try to keep people in remission while we’re working to get towards stem cell transplant as that can sometimes take a few months to get a donor ready, have things ready to move forward with transplant. 

Katherine Banwell:

And what are the options for consolidation therapy?  

Dr. Alice Mims:

Sure. So, options for consolidated chemotherapy are typically based off of what you had initially for induction chemotherapy. So, if it’s more intensive-based regimens, it typically is consolidation with intensive consolidation, cytarabine based regimens.  

For lower intensity regimens, typically consolidation is more continuing therapy on what you started but may have adjustments of the treatment based off of trying to decrease the toxicity now that the patients are in remission. 

Katherine Banwell:

And how are patients monitored in consolidation therapy? 

Dr. Alice Mims:

Sure. So, it definitely is based off of the individual’s type of consolidation chemotherapy or treatment. But most patients, if we feel like the treatment is going to lower blood counts, they have bloodwork twice a week, and we’re watching for things, for side effects for treatment, looking out for risk of infection, giving transfusion support, and then if something happens that we feel like we can’t support patients in an outpatient setting, then we’ll get them back into the hospital if they need to for care. 

Katherine Banwell:

What side effects are you looking for?  

Dr. Alice Mims:

So, most of the side effects with any of the treatments that we give are what we call myelosuppressives. So, it lowers the different types of blood counts.   

So, white blood cell count which increases risk of infection, red blood cells, so, side effects or symptoms from anemia. And then risk of bleeding from low platelet counts.  

Katherine Banwell:

Okay. Maintenance therapy has become more common in other blood cancers particularly in multiple myeloma. Is there a role for maintenance therapy in AML? 

Dr. Alice Mims:

There actually is now, which is something that’s newer that has evolved for acute myeloma leukemia. So, in the context of intensive therapy, we now have oral azacitidine (Onureg), which is a little bit different than some of the IV formulations that we give.  

But for patients who receive intensive induction therapy, get into remission and may receive consolidation but are not able to go onto transplant if they have that immediate or higher risk features, there’s FDA approval for oral azacytidine, which has been shown to improve overall survival and keep people in those remissions for longer. 

More recently, specifically for patients who have a particular type of mutation called FLT3, if they also receive intensive induction therapy with a FLT3 inhibitor added onto that, then their quizartinib was just recently approved as a maintenance therapy for patients with that particular type of AML.  

Katherine Banwell:

Are there emerging AML therapies that patients should know about other than what you just mentioned? 

Dr. Alice Mims:

Sure. So, I think there are a lot of exciting treatments that are up and coming based off of many small molecule inhibitors that are being studied. 

One in particular I would mention that everyone’s very excited about is a class of agents called menin inhibitors.  

And so that’s an oral agent that has been shown to have responses for patients with relapse or refractory AML who have NMP-1 mutations or have something called KNT2A rearrangements. And seeing responses with just a single agent in the relapse refractory setting, it’s been really exciting. And so, I think we’re hopeful that that may become FDA-approved in the near future. And it’s also now being explored in combination with intensive chemotherapies as well as less intensive induction regimens. And so, maybe we can do a better job without brunt treatment by adding these therapies on. 

Katherine Banwell:

That’s exciting news. When it comes to living and thriving with AML, Dr. Mims, managing disease symptoms and treatment side effects is a big part of that. 

Would you talk about how symptoms and side effects can impact life with AML?  

Dr. Alice Mims:

Sure. So, I think from my perspective, what we are always trying to do when we’re moving forward with a treatment plan is of course, get patients into remission, but the purpose of getting into remission is not just to achieve that, but for patients to have quality of life. And so, there needs to be continued dialogue between the patient and the treatment team about how you’re feeling during treatment. Because they’re definitely based off of therapy, different side effects, things that could be not necessarily due to active leukemia anymore. And so there may need to be dose adjustments and other things that we do to the regimens in order to make you feel as good as possible while continuing on treatment. 

Katherine Banwell:

Why is it so important for patients to speak up about any issues they may be having? 

Dr. Alice Mims:

I think it’s important because you’re your own best advocate. Being the patient, being the person who’s living with having this diagnosis and going through the treatment, myself, or other colleagues as physicians, we can have a sense of what may be going on based off of numbers. But we’re not truly going to know how you’re feeling unless you speak up and let us know. And there may be things we could do with supportive medications, dosing adjustments as mentioned, that could help in making you hopefully feel better and less side effects and toxicities from treatment. 

Katherine Banwell:

What are some common symptoms and side effects that you hear about?  

Dr. Alice Mims:

Okay. Sure. So, different side effects that I would say that people can have, people can feel fatigued just from treatment in general. Some of our therapies can cause neuropathy, skin rashes, nausea, vomiting, diarrhea. And so, all of those are important along as mentioned with symptoms you may have from decreased blood counts that we do have interventions that we could implement to help the – make the therapy more tolerable. 

Katherine Banwell:

So, for the side effects like fatigue for example, what do you do about that? 

Dr. Alice Mims:

So, I think it depends on the level of fatigue. Of course, we don’t have – I wish we had a pill that could just make fatigue improve. But if it’s really that the treatment is deriving it, and it’s impeding your quality of life there are dose reductions or things we can do that may help with the level of fatigue you’re experiencing.  

Katherine Banwell:

And what about some of the other side effects. You mentioned diarrhea. 

Dr. Alice Mims:

Sure.  

Katherine Banwell:

How is that handled? 

Dr. Alice Mims:

Yeah. So, for issues from GI complications such as nausea, vomiting, diarrhea, we have really lots of choices for anti-nausea medicines and different combinations we can use or newer antiemetics that can help with that. And from a diarrhea perspective it depends on the treatment. But of course, we want to make sure first and foremost there’s no infection. And if not, then there are good antidiarrheals we could add on to the regiment to help with that as well. 

Katherine Banwell:

Okay. That’s great advice. Thank you. I want to make sure that we get to some of the audience questions. These were sent to us in advance of the program today. Let’s start with this one; Janet wants to know what factors enable a patient to achieve and continue in remission if they are not able to achieve stem cell transplant due to age restrictions.  

Dr. Alice Mims:

So, I think first and foremost, I think it’s very important that there — that patients are aware that there shouldn’t be just strict, stringent cutoffs of age as a requirement for stem cell transplant. And really, there’s a lot of research going on that we should take into account. Physiological age, and there’s ways to measure that just to be sure that stem cell transplant really is not an option. And for patients who stem cell transplant is not an option, I think as we talked about earlier, so there can still be really great treatments that can get patients into remission and ongoing therapies with dosing adjustments again to decrease toxicity and improve quality of life and thinking about things like maintenance therapy as appropriate. 

Katherine Banwell:

What are the age restrictions, and why are they there? 

Dr. Alice Mims:

So, sometimes you will hear age 75.

Really, no one above age 75 should move forward with transplant. And that’s based off of past data where they’ve explored transplant and seen increased toxicity. And from transplant in itself, increased side effects, increased risk of early mortality. And so, I do think it’s important to take the patient as a whole into consideration because again, you could have someone who’s 77 who may be running marathons, and in great shape, and not a lot of other healthcare issues, who may still do really well with treatment. And so, I think that’s – really needs to be taken in account, really the overall picture of health for the patient before making… 

Katherine Banwell:

So, the… 

Dr. Alice Mims:

…just a firm cutoff. 

Katherine Banwell:

Right. Okay. So, it’s not cut and dry. 

Dr. Alice Mims:

Exactly. 

Katherine Banwell:

If you’re 75 or older, then you definitely can’t have stem cell transplant. 

Dr. Alice Mims:

That’s correct. 

Katherine Banwell:

Then you’re looking at everyone individually. 

Dr. Alice Mims:

Yeah. So, it really should be looked at.  

And I still have some patients who will come to me and say, “Oh, I was told I’m 68 years old, I’m not a candidate.” And that always makes me take a step back. And then we kind of have to have that discussion again. And they may still not be a good candidate based off of other comorbidities or healthcare issues, but it shouldn’t just be a number rules you out for having that as an option. 

Katherine Banwell:

Good to know. We received this question from Carl, “What does treatment look like following transplant? And what are doctors looking for when monitoring through blood tests?” 

Dr. Alice Mims:

Sure. So, after transplant, the first three months is pretty intensive of being seen very frequently at your transplant center twice to once a week. You’re also on immunosuppressive medications to try to help prevent issues like graft vs host disease, which can be a complication from transplant. 

And then over time if you’re doing well, we try to start tapering off those immunosuppressive regimens to see if you can tolerate that. And what I say to most of my patients for – who are undergoing transplant, it can take some time to really feel back to being yourself. It can take six months, it can take a year or longer. And sometimes your normal is a new normal based off of how you do and the side effects of the transplant in itself. So, you may not go back to if you’re here before transplant and before your diagnosis, it may be that this is your new normal. Just so people can be prepared and know what they’re signing up for.  

Katherine Banwell:

And with the blood testing, what are you looking for when you’re monitoring a patient?  

Dr. Alice Mims:

Sure. There are a few different things that we’re looking for when monitoring patients. So, one, making sure that the stem cells or the graft from the donor are recovering. 

You want to see that blood counts, levels of white blood cells, red blood cells, platelets are getting to normal levels. You’re also assessing and making sure you’re not seeing signs of relapse. You’re checking levels of donor cells versus the patient cells within the stem cell — sorry, within the stem cell compartments. And so, we’re taking all of those into account as well as checking organ function and making sure there’s no signs of potential graft versus host disease as well. 

Katherine Banwell:

Katrina sent in this question; do you have any advice for dealing with a general oncologist who does not exactly follow my AML doctor’s recommendations? I see a local oncologist and an AML specialist guides my care. 

Dr. Alice Mims:

I think that’s a tough question. And so, I think I’ll answer that if – maybe two different ways. 

So, one, I think sometimes it’s hard when you’re the local community oncologist, and you’re there for the day-to-day care. And so there may need to be treatment adjustments and other things that you need to do in that moment or time to help make sure that toxicities are not too severe or are helping the patient as you’re seeing them day-to-day. And it may not be easy to involve the specialist right there in the moment. But I think if there are bigger issues as far as overall goals, overall communication, it should be that both are able to communicate well with each other. They should be able to communicate via email, via text message. That’s what I do with a lot of my community partners. And it’s always important that you as a patient feel confident in your care. And so, if that trust is not there that things are being followed, then it may be important to look and see if there’s another physician who you do feel comfortable with proceeding with your care with. 

Katherine Banwell:

And what do you tell patients when they’re not feeling comfortable with their care team or their oncologist or their general oncologist? What do you say to them to give them some confidence to find somebody else who they feel more comfortable with? 

Dr. Alice Mims:

Sure. So, I’ll just say from my perspective. So, if I’m seeing a patient and they may have questions, they may not feel comfortable, they may need more time. And I always think it’s important if you want a second opinion, whether it’s at a specialist level, whether it’s in a community oncology private setting, that should not be offensive to the physician.  

If that makes the patient feel more comfortable in what they’re doing with their care, that’s how they should move forward. And it should be what they feel like is best. If a physician takes that personally or is offended by it, I think that’s more of their problem as opposed to anything that you’re doing wrong.  

Katherine Banwell:

Okay. Thank you for that. Ryan wants to know; I’m a year and a half post-transplant, how can you tell if the aches and pains in your joints are normal aging, host vs graft disease, the AML returning, or even something else? 

Dr. Alice Mims:

So, I think that’s also a difficult question to answer because it really is patient dependent. And so, I think if you’re having new joint aches or pains, it’s always important to reach out to your transplant team to make sure that – it could be any of the above.. 

And so you’re doing the appropriate workup with lab work, imaging, things that would be appropriate or seeing certain specialists. Maybe orthopedist if needed because it could be I’d say less likely leukemic relapse, but still want to be sure. But it could be definitely complications from GVHD or there’s some joint issues that can evolve post-transplant, especially for people who are on long-term immunosuppressant medications. Or it could be the normal effects of aging. So, it’s always good to have that reassurance. 

Katherine Banwell:

Let’s talk a little bit about mental health resources. Managing the worry associated with a diagnosis or concerns about relapse, or even various side effects can lead to emotional symptoms like anxiety and fear.  

Why is it important for people with AML to share how they’re feeling with their healthcare team? 

Dr. Alice Mims:

So, I think it’s very important because, one, all of those feelings are normal feelings. I think they’re sometimes that from going through such a rapid diagnosis and then having to start treatment pretty quickly and going through all the ups and downs with these types of diagnosis can really lead to for some patients PTSD-type symptoms. And then there are also things that can evolve over time where their anxiety or even survivorship guilt as you go if you move forward and are doing well where you may have some friends or people you met along the way who may not have had as good outcomes. And so, there are resources available based off of where you are.  

But for survivorship, oncology specific counseling to deal with some of these feelings that are understandable and normal for what patients have been through. 

Katherine Banwell:

Can a social worker help? And are there other people on the healthcare team who can support a patient’s emotional needs? 

Dr. Alice Mims:

Oh, absolutely. So, I think it’s really place-dependent on where you are but yes, absolutely. Social workers are a great resource for patients. There may be other collaborative teams based off of where you’re receiving your treatment that may be available that are maybe patient support groups where you can go and be with other patients or Facebook, social media support groups. And I think all those can be very helpful. And I know at least at our center, we also have patient mentors who have been through and gotten through to the other side of transplant or whatnot who are great resources because they’ve lived and experienced it. 

And I think that’s just as a physician, I can talk about things that I don’t have that personal experience having lived through it. And I think that’s very important — 

Katherine Banwell:

Yeah. It’s a… 

Dr. Alice Mims:

…to be able to have somebody to talk to. Yeah. 

Katherine Banwell:

Yeah. What about the financial aspect of treatments? There are many people who would find it difficult to find and maybe they don’t have insurance, or their insurance doesn’t cover a lot. How do you help patients who are dealing with financial restrictions?  

Dr. Alice Mims:

Sure. So, I think that we’re fortunate here because we have a lot of support staff to help patients with our financial counseling team. We also have people within the medication assistance programs who can help find foundation grants to help with medication support, travel support. 

I think for patients who may not have those things available at their individual center, The Leukemia & Lymphoma Society is a great place to reach out for.  

And there are other foundations as well who at least may have navigators to help patients figure out other resources or funding available. 

Katherine Banwell:

Yeah. Okay. That’s really good information, Dr. Mims. Thank you. And please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future programs. Well, Dr. Mims as we close out our program, I wanted to get your thoughts on where we stand with progress in AML care. Are there advances in research treatment that you’re hopeful about? 

Dr. Alice Mims:

Yes. I would say from even when I finished fellowship 10 years ago, not to state my age, but we had essentially about three treatments at that time. 

Now in the past five years there have been I think maybe 11 different new drugs that have been approved for a acute myeloma leukemia. And so, I think we’re just on the precipice of really evolving to have individualized care. Hopefully have more curative options for patients. So, I’m really excited for the time we’re in right now where I even hope we’ll be in the next five years for patients. 

Katherine Banwell:

That’s an encouraging message to leave the audience with, Dr. Mims. Thank you so much for joining us today. 

Dr. Alice Mims:

Thank you so much for letting me be here with you today. 

Katherine Banwell:

And thank you to all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.   

Managing Life With AML | What You Should Know About Care and Treatment

Managing Life With AML | What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo

What do you need to know when it comes to managing life with acute myeloid leukemia (AML)? In this webinar, Dr. Alice Mims, an AML specialist and researcher, discusses how treatment decisions are made and how test results may impact therapy. Dr. Mims will shares the latest advances in research and key advice for living well with AML.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims.

Download Resource Guide

See More from Thrive AML

Related Resources:

AML Treatment Decisions | Understanding Factors That Impact Your Options

AML Specialists and Second Opinions Expert Advice to Patients

How Can You Thrive With AML Advice for Navigating Care.


Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for today. Today’s program is a continuation of our Thrive series. And we’re going to discuss navigating life with AML, and how you can engage in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, joining us today is Dr. Alice Mims.  

Dr. Mims, welcome. Would you please introduce yourself? 

Dr. Alice Mims:

Yeah, sure. Thank you, Katherine. I’m Alice Mims. I’m a physician and associate professor at Ohio State University. And also, the section head for the myeloid and acute leukemia program within our division of hematology. 

Katherine Banwell:

Thank you so much for taking the time to join us today, Dr. Mims. We start all of our webinars in our thrive series with the same question; in your experience, what does it mean to thrive with AML? 

Dr. Alice Mims:

Sure, I think that’s a great question. So, really for me, I think thriving with AML is very patient- or person-dependent. It really depends on making sure that your treatment goals align with your care. And so that means really being an active participant in your diagnosis, understanding the disease process, and making sure that your care team really understands what your overall goals are for your treatment. 

Katherine Banwell:

Thank you for that because it helps us to understand as we move through the program today. One part of thriving with AML is finding a treatment approach that manages your disease and fits with your lifestyle. Before we talk about therapy, can you tell us how treatment goals are established for an individual patient? 

Dr. Alice Mims:

Sure. So, for individual patients I think it’s very important that there is an initial discussion that doesn’t feel too shortened that you can have time with your care team to really go into depth about the diagnosis, about the specifics of your particular subtype of acute myeloid leukemia, understanding the treatment options, and then being given time allowed to reflect on all of that information. So, then you can come back and have your questions better answered that may come from that initial discussion. 

And then help you with your team make a decision based on that information that works best for you. 

Katherine Banwell:

Outside of patient preference, what other factors do you take into account when working with a patient to decide on a treatment plan?  

Dr. Alice Mims:

Sure. So, there are multiple different factors that we try to take into account. Again, yeah most importantly what patients’ goals are like you mentioned, but those include overall health, including different comorbidities, so what other healthcare diagnoses, medications are you taking, what are the patient’s age, thinking about that for long-term goals, overall support from loved ones, family to — just because care can be really involved. And then in particular, thinking about specific features of that individual patient’s AML, including molecular, genetic features of the leukemia. 

Katherine Banwell:

Well, let’s talk more in depth about the test results you just mentioned. 

What is the test for genetic markers? And how is it conducted? 

Dr. Alice Mims:

So, there are a few different tests that we use under that scope of genetic markers. So, those include looking at chromosomal abnormalities of the DNA. So, with cytogenetics, and then also more specific prose where we call FISH testing. And then also we look for specific gene mutations through next generation sequencing, or PCR testing. And so, we use all of those results together to give us the most information we can about that individual’s leukemia. 

Katherine Banwell:

How has molecular testing revolutionized AML care?  

Dr. Alice Mims:

Oh gracious. It’s really done such – so much for leukemia. And just things are so different even where they were five years ago because of having molecular mutations, that information available. 

So, it helps with discussing prognosis. So, we know that different molecular features can tell us about curative intent and what are the treatment steps we would need to take to give the best chance long-term. And then also now, we’ve evolved to where we have directed therapies that can target mutations or the proteins that arise from those mutations with therapeutic options. 

Katherine Banwell:

Is this testing standard following an AML diagnosis? 

Dr. Alice Mims:

It is standard following an AML diagnosis. That’s recommended within all of the guidelines with patients and really should be done for all patients at initial diagnosis. 

Katherine Banwell:

Can genetic markers or mutations change over time? For example, if a patient relapses, should molecular testing be done again? 

Dr. Alice Mims:

Yes, absolutely. Mutations can evolve. It’s something we call clonal evolution of the leukemia. 

And so you can have mutations that could be present at diagnosis that may no longer be present. Or the opposite can occur where you have new mutations that can appear. And that can lead to different options for treatment. So, it’s very important to retest at time of relapse. 

Katherine Banwell:

What advice do you have for patients who want to ensure that they’ve actually undergone molecular testing? What questions should they be asking their healthcare team? 

Dr. Alice Mims:

I think it’s definitely important to bring this up with the healthcare team. And it should be something at diagnosis and relapse to ask, what are the cytogenetics, what do they look like now, what do the gene mutations, and really as mentioned before, it’s so crucial in talking about prognosis, talking about treatment options that if it doesn’t come up, it’s really something that you should take a pause and try to go back to readdress with your team. 

Katherine Banwell:

I’d like to move on to treatment now, Dr. Mims. And, of course, treatment takes place in phases for AML. The first is induction therapy. Can you start by defining induction therapy for our audience? 

Dr. Alice Mims:

Sure. So, induction therapy is really terminology that we use to talk about initial therapy for someone with a new diagnosis. So, we can have intensive induction therapies, and non-intensive induction therapies. But the goal for either of those types of treatment is to get the leukemia into remission. 

So, to talk about that in a little bit more detail, for intensive induction regimens, those typically involve cytotoxic chemotherapy. So, you may hear terminology like, “7 + 3 induction,” or “high-dose cytarabine regimens,” but those are typically more intensive regimens that we use that can have increased side effects but may be very important based off the type of acute leukemia. 

And then for non-intensive based regimens, one of the standards has really evolved to be venetoclax (Venclexta) and azacitidine (Vidaza) as a non-intensive regimen that can work very well for a majority of patients. And there are some off shoots of that as well. 

Katherine Banwell:

Okay. And when does stem cell transplant come into play? 

Dr. Alice Mims:

Sure. So, stem cell transplant is something that we all think about at the beginning for anyone with a new diagnosis of acute myeloid leukemia where as we’re working to get back genomic information about the individual’s acute leukemia, we may go ahead and start looking for different donors, doing typing, just in case that’s something that we need as far as someone’s therapy. 

But typically we reserve stem cell transplant for patients who have either intermediate or high-risk features of their AML. Or who may have even favorable respite are not responding as well as we would like when looking at the depth of remission. And so, we always want  to be prepared in case that’s something we need to move forward with as part of their care, if the goal of their treatment is for curative intent. 

Katherine Banwell:

Let’s talk about what happens after the initial phase of treatment. What’s the purpose of consolidation therapy? 

Dr. Alice Mims:

Sure. So, there are a few different purposes we can use consolidation therapy for. So, for patients – consolidation therapy is used for patients who have achieved remission. And then it’s either to try to hopefully get them cure of their AML. The patients have more favorable risk features of their AML and cure is an option through just chemotherapy alone. 

Or it can be used to try to keep people in remission while we’re working to get towards stem cell transplant as that can sometimes take a few months to get a donor ready, have things ready to move forward with transplant. 

Katherine Banwell:

And what are the options for consolidation therapy?  

Dr. Alice Mims:

Sure. So, options for consolidated chemotherapy are typically based off of what you had initially for induction chemotherapy. So, if it’s more intensive-based regimens, it typically is consolidation with intensive consolidation, cytarabine based regimens.  

For lower intensity regimens, typically consolidation is more continuing therapy on what you started but may have adjustments of the treatment based off of trying to decrease the toxicity now that the patients are in remission. 

Katherine Banwell:

And how are patients monitored in consolidation therapy? 

Dr. Alice Mims:

Sure. So, it definitely is based off of the individual’s type of consolidation chemotherapy or treatment. But most patients, if we feel like the treatment is going to lower blood counts, they have bloodwork twice a week, and we’re watching for things, for side effects for treatment, looking out for risk of infection, giving transfusion support, and then if something happens that we feel like we can’t support patients in an outpatient setting, then we’ll get them back into the hospital if they need to for care. 

Katherine Banwell:

What side effects are you looking for?  

Dr. Alice Mims:

So, most of the side effects with any of the treatments that we give are what we call myelosuppressives. So, it lowers the different types of blood counts.   

So, white blood cell count which increases risk of infection, red blood cells, so, side effects or symptoms from anemia. And then risk of bleeding from low platelet counts.  

Katherine Banwell:

Okay. Maintenance therapy has become more common in other blood cancers particularly in multiple myeloma. Is there a role for maintenance therapy in AML? 

Dr. Alice Mims:

There actually is now, which is something that’s newer that has evolved for acute myeloma leukemia. So, in the context of intensive therapy, we now have oral azacitidine (Onureg), which is a little bit different than some of the IV formulations that we give.  

But for patients who receive intensive induction therapy, get into remission and may receive consolidation but are not able to go onto transplant if they have that immediate or higher risk features, there’s FDA approval for oral azacytidine, which has been shown to improve overall survival and keep people in those remissions for longer. 

More recently, specifically for patients who have a particular type of mutation called FLT3, if they also receive intensive induction therapy with a FLT3 inhibitor added onto that, then their quizartinib was just recently approved as a maintenance therapy for patients with that particular type of AML.  

Katherine Banwell:

Are there emerging AML therapies that patients should know about other than what you just mentioned? 

Dr. Alice Mims:

Sure. So, I think there are a lot of exciting treatments that are up and coming based off of many small molecule inhibitors that are being studied. 

One in particular I would mention that everyone’s very excited about is a class of agents called menin inhibitors.  

And so that’s an oral agent that has been shown to have responses for patients with relapse or refractory AML who have NMP-1 mutations or have something called KNT2A rearrangements. And seeing responses with just a single agent in the relapse refractory setting, it’s been really exciting. And so, I think we’re hopeful that that may become FDA-approved in the near future. And it’s also now being explored in combination with intensive chemotherapies as well as less intensive induction regimens. And so, maybe we can do a better job without brunt treatment by adding these therapies on. 

Katherine Banwell:

That’s exciting news. When it comes to living and thriving with AML, Dr. Mims, managing disease symptoms and treatment side effects is a big part of that. 

Would you talk about how symptoms and side effects can impact life with AML?  

Dr. Alice Mims:

Sure. So, I think from my perspective, what we are always trying to do when we’re moving forward with a treatment plan is of course, get patients into remission, but the purpose of getting into remission is not just to achieve that, but for patients to have quality of life. And so, there needs to be continued dialogue between the patient and the treatment team about how you’re feeling during treatment. Because they’re definitely based off of therapy, different side effects, things that could be not necessarily due to active leukemia anymore. And so there may need to be dose adjustments and other things that we do to the regimens in order to make you feel as good as possible while continuing on treatment. 

Katherine Banwell:

Why is it so important for patients to speak up about any issues they may be having? 

Dr. Alice Mims:

I think it’s important because you’re your own best advocate. Being the patient, being the person who’s living with having this diagnosis and going through the treatment, myself, or other colleagues as physicians, we can have a sense of what may be going on based off of numbers. But we’re not truly going to know how you’re feeling unless you speak up and let us know. And there may be things we could do with supportive medications, dosing adjustments as mentioned, that could help in making you hopefully feel better and less side effects and toxicities from treatment. 

Katherine Banwell:

What are some common symptoms and side effects that you hear about?  

Dr. Alice Mims:

Okay. Sure. So, different side effects that I would say that people can have, people can feel fatigued just from treatment in general. Some of our therapies can cause neuropathy, skin rashes, nausea, vomiting, diarrhea. And so, all of those are important along as mentioned with symptoms you may have from decreased blood counts that we do have interventions that we could implement to help the – make the therapy more tolerable. 

Katherine Banwell:

So, for the side effects like fatigue for example, what do you do about that? 

Dr. Alice Mims:

So, I think it depends on the level of fatigue. Of course, we don’t have – I wish we had a pill that could just make fatigue improve. But if it’s really that the treatment is deriving it, and it’s impeding your quality of life there are dose reductions or things we can do that may help with the level of fatigue you’re experiencing.  

Katherine Banwell:

And what about some of the other side effects. You mentioned diarrhea. 

Dr. Alice Mims:

Sure.  

Katherine Banwell:

How is that handled? 

Dr. Alice Mims:

Yeah. So, for issues from GI complications such as nausea, vomiting, diarrhea, we have really lots of choices for anti-nausea medicines and different combinations we can use or newer antiemetics that can help with that. And from a diarrhea perspective it depends on the treatment. But of course, we want to make sure first and foremost there’s no infection. And if not, then there are good antidiarrheals we could add on to the regiment to help with that as well. 

Katherine Banwell:

Okay. That’s great advice. Thank you. I want to make sure that we get to some of the audience questions. These were sent to us in advance of the program today. Let’s start with this one; Janet wants to know what factors enable a patient to achieve and continue in remission if they are not able to achieve stem cell transplant due to age restrictions.  

Dr. Alice Mims:

So, I think first and foremost, I think it’s very important that there — that patients are aware that there shouldn’t be just strict, stringent cutoffs of age as a requirement for stem cell transplant. And really, there’s a lot of research going on that we should take into account. Physiological age, and there’s ways to measure that just to be sure that stem cell transplant really is not an option. And for patients who stem cell transplant is not an option, I think as we talked about earlier, so there can still be really great treatments that can get patients into remission and ongoing therapies with dosing adjustments again to decrease toxicity and improve quality of life and thinking about things like maintenance therapy as appropriate. 

Katherine Banwell:

What are the age restrictions, and why are they there? 

Dr. Alice Mims:

So, sometimes you will hear age 75.

Really, no one above age 75 should move forward with transplant. And that’s based off of past data where they’ve explored transplant and seen increased toxicity. And from transplant in itself, increased side effects, increased risk of early mortality. And so, I do think it’s important to take the patient as a whole into consideration because again, you could have someone who’s 77 who may be running marathons, and in great shape, and not a lot of other healthcare issues, who may still do really well with treatment. And so, I think that’s – really needs to be taken in account, really the overall picture of health for the patient before making… 

Katherine Banwell:

So, the… 

Dr. Alice Mims:

…just a firm cutoff. 

Katherine Banwell:

Right. Okay. So, it’s not cut and dry. 

Dr. Alice Mims:

Exactly. 

Katherine Banwell:

If you’re 75 or older, then you definitely can’t have stem cell transplant. 

Dr. Alice Mims:

That’s correct. 

Katherine Banwell:

Then you’re looking at everyone individually. 

Dr. Alice Mims:

Yeah. So, it really should be looked at.  

And I still have some patients who will come to me and say, “Oh, I was told I’m 68 years old, I’m not a candidate.” And that always makes me take a step back. And then we kind of have to have that discussion again. And they may still not be a good candidate based off of other comorbidities or healthcare issues, but it shouldn’t just be a number rules you out for having that as an option. 

Katherine Banwell:

Good to know. We received this question from Carl, “What does treatment look like following transplant? And what are doctors looking for when monitoring through blood tests?” 

Dr. Alice Mims:

Sure. So, after transplant, the first three months is pretty intensive of being seen very frequently at your transplant center twice to once a week. You’re also on immunosuppressive medications to try to help prevent issues like graft vs host disease, which can be a complication from transplant. 

And then over time if you’re doing well, we try to start tapering off those immunosuppressive regimens to see if you can tolerate that. And what I say to most of my patients for – who are undergoing transplant, it can take some time to really feel back to being yourself. It can take six months, it can take a year or longer. And sometimes your normal is a new normal based off of how you do and the side effects of the transplant in itself. So, you may not go back to if you’re here before transplant and before your diagnosis, it may be that this is your new normal. Just so people can be prepared and know what they’re signing up for.  

Katherine Banwell:

And with the blood testing, what are you looking for when you’re monitoring a patient?  

Dr. Alice Mims:

Sure. There are a few different things that we’re looking for when monitoring patients. So, one, making sure that the stem cells or the graft from the donor are recovering. 

You want to see that blood counts, levels of white blood cells, red blood cells, platelets are getting to normal levels. You’re also assessing and making sure you’re not seeing signs of relapse. You’re checking levels of donor cells versus the patient cells within the stem cell — sorry, within the stem cell compartments. And so, we’re taking all of those into account as well as checking organ function and making sure there’s no signs of potential graft versus host disease as well. 

Katherine Banwell:

Katrina sent in this question; do you have any advice for dealing with a general oncologist who does not exactly follow my AML doctor’s recommendations? I see a local oncologist and an AML specialist guides my care. 

Dr. Alice Mims:

I think that’s a tough question. And so, I think I’ll answer that if – maybe two different ways. 

So, one, I think sometimes it’s hard when you’re the local community oncologist, and you’re there for the day-to-day care. And so there may need to be treatment adjustments and other things that you need to do in that moment or time to help make sure that toxicities are not too severe or are helping the patient as you’re seeing them day-to-day. And it may not be easy to involve the specialist right there in the moment. But I think if there are bigger issues as far as overall goals, overall communication, it should be that both are able to communicate well with each other. They should be able to communicate via email, via text message. That’s what I do with a lot of my community partners. And it’s always important that you as a patient feel confident in your care. And so, if that trust is not there that things are being followed, then it may be important to look and see if there’s another physician who you do feel comfortable with proceeding with your care with. 

Katherine Banwell:

And what do you tell patients when they’re not feeling comfortable with their care team or their oncologist or their general oncologist? What do you say to them to give them some confidence to find somebody else who they feel more comfortable with? 

Dr. Alice Mims:

Sure. So, I’ll just say from my perspective. So, if I’m seeing a patient and they may have questions, they may not feel comfortable, they may need more time. And I always think it’s important if you want a second opinion, whether it’s at a specialist level, whether it’s in a community oncology private setting, that should not be offensive to the physician.  

If that makes the patient feel more comfortable in what they’re doing with their care, that’s how they should move forward. And it should be what they feel like is best. If a physician takes that personally or is offended by it, I think that’s more of their problem as opposed to anything that you’re doing wrong.  

Katherine Banwell:

Okay. Thank you for that. Ryan wants to know; I’m a year and a half post-transplant, how can you tell if the aches and pains in your joints are normal aging, host vs graft disease, the AML returning, or even something else? 

Dr. Alice Mims:

So, I think that’s also a difficult question to answer because it really is patient dependent. And so, I think if you’re having new joint aches or pains, it’s always important to reach out to your transplant team to make sure that – it could be any of the above.. 

And so you’re doing the appropriate workup with lab work, imaging, things that would be appropriate or seeing certain specialists. Maybe orthopedist if needed because it could be I’d say less likely leukemic relapse, but still want to be sure. But it could be definitely complications from GVHD or there’s some joint issues that can evolve post-transplant, especially for people who are on long-term immunosuppressant medications. Or it could be the normal effects of aging. So, it’s always good to have that reassurance. 

Katherine Banwell:

Let’s talk a little bit about mental health resources. Managing the worry associated with a diagnosis or concerns about relapse, or even various side effects can lead to emotional symptoms like anxiety and fear.  

Why is it important for people with AML to share how they’re feeling with their healthcare team? 

Dr. Alice Mims:

So, I think it’s very important because, one, all of those feelings are normal feelings. I think they’re sometimes that from going through such a rapid diagnosis and then having to start treatment pretty quickly and going through all the ups and downs with these types of diagnosis can really lead to for some patients PTSD-type symptoms. And then there are also things that can evolve over time where their anxiety or even survivorship guilt as you go if you move forward and are doing well where you may have some friends or people you met along the way who may not have had as good outcomes. And so, there are resources available based off of where you are.  

But for survivorship, oncology specific counseling to deal with some of these feelings that are understandable and normal for what patients have been through. 

Katherine Banwell:

Can a social worker help? And are there other people on the healthcare team who can support a patient’s emotional needs? 

Dr. Alice Mims:

Oh, absolutely. So, I think it’s really place-dependent on where you are but yes, absolutely. Social workers are a great resource for patients. There may be other collaborative teams based off of where you’re receiving your treatment that may be available that are maybe patient support groups where you can go and be with other patients or Facebook, social media support groups. And I think all those can be very helpful. And I know at least at our center, we also have patient mentors who have been through and gotten through to the other side of transplant or whatnot who are great resources because they’ve lived and experienced it. 

And I think that’s just as a physician, I can talk about things that I don’t have that personal experience having lived through it. And I think that’s very important — 

Katherine Banwell:

Yeah. It’s a… 

Dr. Alice Mims:

…to be able to have somebody to talk to. Yeah. 

Katherine Banwell:

Yeah. What about the financial aspect of treatments? There are many people who would find it difficult to find and maybe they don’t have insurance, or their insurance doesn’t cover a lot. How do you help patients who are dealing with financial restrictions?  

Dr. Alice Mims:

Sure. So, I think that we’re fortunate here because we have a lot of support staff to help patients with our financial counseling team. We also have people within the medication assistance programs who can help find foundation grants to help with medication support, travel support. 

I think for patients who may not have those things available at their individual center, The Leukemia & Lymphoma Society is a great place to reach out for.  

And there are other foundations as well who at least may have navigators to help patients figure out other resources or funding available. 

Katherine Banwell:

Yeah. Okay. That’s really good information, Dr. Mims. Thank you. And please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future programs. Well, Dr. Mims as we close out our program, I wanted to get your thoughts on where we stand with progress in AML care. Are there advances in research treatment that you’re hopeful about? 

Dr. Alice Mims:

Yes. I would say from even when I finished fellowship 10 years ago, not to state my age, but we had essentially about three treatments at that time. 

Now in the past five years there have been I think maybe 11 different new drugs that have been approved for a acute myeloma leukemia. And so, I think we’re just on the precipice of really evolving to have individualized care. Hopefully have more curative options for patients. So, I’m really excited for the time we’re in right now where I even hope we’ll be in the next five years for patients. 

Katherine Banwell:

That’s an encouraging message to leave the audience with, Dr. Mims. Thank you so much for joining us today. 

Dr. Alice Mims:

Thank you so much for letting me be here with you today. 

Katherine Banwell:

And thank you to all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.   

Phases of AML Therapy | Understanding Treatment Options

Phases of AML Therapy | Understanding Treatment Options from Patient Empowerment Network on Vimeo.

What are the types and phases of acute myeloid leukemia (AML) treatment? Dr. Alice Mims, an AML specialist, defines induction, consolidation, and maintenance therapy for patients. Dr. Mims also explains the role of stem cell transplant and discusses promising new AML therapies.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims

See More from Thrive AML

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How Can You Thrive With AML Advice for Navigating Care.

New and Emerging AML Therapies Being Studied in Clinical Trials

New and Emerging AML Therapies Being Studied in Clinical Trials


Transcript:

Katherine Banwell:

I’d like to move on to treatment now, Dr. Mims. And, of course, treatment takes place in phases for AML. The first is induction therapy. Can you start by defining induction therapy for our audience?  

Dr. Alice Mims:

Sure. So, induction therapy is really terminology that we use to talk about initial therapy for someone with a new diagnosis. So, we can have intensive induction therapies and non-intensive induction therapies. But the goal for either of those types of treatment is to get the leukemia into remission.  

Katherine Banwell:

And what are the available treatment options for induction therapy?  

Dr. Alice Mims:

So, to talk about that in a little bit more detail, for intensive induction regimens, those typically involve cytotoxic chemotherapy. So, you may hear terminology like, “7 + 3 induction,” or “high-dose cytarabine regimens,” but those are typically more intensive regimens that we use that can have increased side effects but may be very important based off the type of acute leukemia. 

And then for non-intensive based regimens, one of the standards has really evolved to be venetoclax (Venclexta) and azacitidine (Vidaza) as a non-intensive regimen that can work very well for a majority of patients. And there are some off shoots of that as well. 

Katherine Banwell:

Okay. And when does stem cell transplant come into play? 

Dr. Alice Mims:

Sure. So, stem cell transplant is something that we all think about at the beginning for anyone with a new diagnosis of acute myeloid leukemia where as we’re working to get back genomic information about the individual’s acute leukemia, we may go ahead and start looking for different donors, doing typing, just in case that’s something that we need as far as someone’s therapy.  

But typically we reserve stem cell transplant for patients who have either intermediate or high-risk features of their AML. Or who may have even favorable respite are not responding as well as we would like when looking at the depth of remission. And so, we always want  to be prepared in case that’s something we need to move forward with as part of their care, if the goal of their treatment is for curative intent. 

Katherine Banwell:

Let’s talk about what happens after the initial phase of treatment. What’s the purpose of consolidation therapy? 

Dr. Alice Mims:

Sure. So, there are a few different purposes we can use consolidation therapy for. So, for patients – consolidation therapy is used for patients who have achieved remission. And then it’s either to try to hopefully get them cure of their AML. The patients have more favorable risk features of their AML and cure is an option through just chemotherapy alone.  

Or it can be used to try to keep people in remission while we’re working to get towards stem cell transplant as that can sometimes take a few months to get a donor ready, have things ready to move forward with transplant. 

Katherine Banwell:

And what are the options for consolidation therapy?  

Dr. Alice Mims:

Sure. So, options for consolidated chemotherapy are typically based off of what you had initially for induction chemotherapy. So, if it’s more intensive-based regimens, it typically is consolidation with intensive consolidation, cytarabine-based (Cytosar-U) regimens.  

For lower intensity regimens, typically consolidation is more continuing therapy on what you started but may have adjustments of the treatment based off of trying to decrease the toxicity now that the patients are in remission. 

Katherine Banwell:

And how are patients monitored in consolidation therapy? 

Dr. Alice Mims:

Sure. So, it definitely is based off of the individual’s type of consolidation chemotherapy or treatment. But most patients, if we feel like the treatment is going to lower blood counts, they have bloodwork twice a week, and we’re watching for things, for side effects for treatment, looking out for risk of infection, giving transfusion support, and then if something happens that we feel like we can’t support patients in an outpatient setting, then we’ll get them back into the hospital if they need to for care. 

Katherine Banwell:

What side effects are you looking for? 

Dr. Alice Mims:

So, most of the side effects with any of the treatments that we give are what we call myelosuppressives. So, it lowers the different types of blood counts.  

So, white blood cell count which increases risk of infection, red blood cells, so, side effects or symptoms from anemia. And then risk of bleeding from low platelet counts.  

Katherine Banwell:

Okay. Maintenance therapy has become more common in other blood cancers particularly in multiple myeloma. Is there a role for maintenance therapy in AML? 

Dr. Alice Mims:

There actually is now, which is something that’s newer that has evolved for acute myeloma leukemia. So, in the context of intensive therapy, we now have oral azacitidine (Onureg), which is a little bit different than some of the IV formulations that we give.  

But for patients who receive intensive induction therapy, get into remission and may receive consolidation but are not able to go onto transplant if they have that immediate or higher risk features, there’s FDA approval for oral azacytidine, which has been shown to improve overall survival and keep people in those remissions for longer. 

More recently, specifically for patients who have a particular type of mutation called FLT3, if they also receive intensive induction therapy with a FLT3 inhibitor added onto that, then their quizartinib (Vanflyta) was just recently approved as a maintenance therapy for patients with that particular type of AML. 

Katherine Banwell:

Are there emerging AML therapies that patients should know about other than what you just mentioned? 

Dr. Alice Mims:

Sure. So, I think there are a lot of exciting treatments that are up and coming based off of many small molecule inhibitors that are being studied.  

One in particular I would mention that everyone’s very excited about is a class of agents called menin inhibitors.  

And so that’s an oral agent that has been shown to have responses for patients with relapsed or refractory AML who have NMP-1 mutations or have something called KNT2A rearrangements. And seeing responses with just a single agent in the relapsed/refractory setting, it’s been really exciting. And so, I think we’re hopeful that that may become FDA-approved in the near future. And it’s also now being explored in combination with intensive chemotherapies as well as less intensive induction regimens. And so, maybe we can do a better job with upfront treatment by adding these therapies on.  

AML Treatment Decisions | Understanding Factors That Impact Your Options

AML Treatment Decisions | Understanding Factors That Impact Your Options from Patient Empowerment Network on Vimeo.

An acute myeloid leukemia (AML) diagnosis can be different for each individual patient, so how is a treatment approach determined? AML specialist Dr. Jacqueline Garcia provides an overview of factors taken into consideration when choosing therapy, including age, overall health, and the patient’s preference. 

Dr. Jacqueline Garcia is an oncologist and AML researcher at the Dana-Farber Cancer Institute. Learn more about Dr. Garcia.

See More from Thrive AML

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Transcript:

Katherine Banwell:

With all the treatment options available, how do you decide who gets what? Tell us what is considered when choosing treatment for a patient. 

Dr. Jacqueline Garcia:

When I – this is a complicated question, because it’s not like you follow any particular algorithm. But when I meet a patient, I make a decision on what’s important to the patient and what’s  their goal. If I know – I need to understand their overall health to get a sense of are there ongoing competing risk factors that are active and more likely to impede with response, ability to deliver chemo, ability to get to transplant, something that tells me that’s not a possibility, or is their age too advanced – meaning greater than 75 – where we know that some of the treatments are not safe to deliver in that setting?   

So, I take a look at a patient’s overall health and age to make a decision. I take a look at bone marrow biopsy and lab findings to understand the flavor of their leukemia, from chromosomes to mutations. And because I am familiar with the data to give me a sense of what’s safe, what’s tolerable, and importantly what types of diseases, or subtypes of AML, would respond to one therapy over another, that’s how I formulate a recommendation.  

And based on all of that, all together, I’ll talk to them about treating the AML in steps. The first step is getting them into a remission, which can be done regardless of therapy type. That means to get their bone marrow under control, blood counts to recover. The second step, which is a more involved conversation that I often give a little bit of a hint of, but I go into greater detail over time, because we will see each other quite a lot, whether in the hospital or in clinic, is how to keep them in remission.  

And that’s where details about things like transplant come into play. I do my best to not overwhelm them, because when a patient hears the word transplant – and that’s often what they hear from family and friends because that’s what you can Google – they don’t know that there are many things, or many weeks of therapy, that have to happen in advance of transplant even being considered or happening. And transplant can’t even happen until someone’s in remission.  

But that is always on the forefront of a leukemia doctor’s mind, “Can I bring this patient to a transplantation? How successful will I be and what else do I need to give them to get them there sooner, safer, with a deeper response?” So, that way transplant could be successful. Transplant, by the way, is when we give a patient someone else’s stem cells that match their HLA typing, or their white blood cell signature.  

And it helps us to use someone else’s immune system to completely irradicate any microscopic leftover leukemia in a patient. But that is only successful when patients have good disease control or remissions. And that is only also successful if we have a donor for the patient, both of which  require at least several weeks to a couple of months of therapy. But that process is always initiated and ongoing in the background. And so, we often do this in piecemeal, because getting a diagnosis is already overwhelming. Learning about treatment is overwhelming.  

Learning about the frequency of labs, transfusions, being hospitalized, and then details about what a transplant would entail can be also overwhelming. But a lot of family and friends like to ask, because they feel like that is one way they might be able to help a patient. So, I know that they often eagerly ask the patient, “Well, what about this? How can I help?”  

Katherine Banwell:

Right. I can imagine that patient preference is also considered. But what kind of questions should patients ask about their treatment regimen?  

Dr. Jacqueline Garcia:

I always tell patients that I care very much about things like travel, hotels, all that jazz. But I always tell them let’s first talk about their health, what treatment I would recommend based on the available options and what their disease would mostly respond to, because I want it to be successful. And I always tell them let’s reserve questions on how it’s going to be done for last. I call that the logistics. I will never bring up or recommend something that could never be possible. But that being said, I try not to let the commute determine the decision.  

Whether or not there needs to be a hospitalization versus a hotel stay. I always consider then the background, but that financial decision should not drive the best treatment choice for a patient. Very fortunately, we’re in a country where patients have the ability – often, not always – to seek second opinions or to travel to academic centers.  

And because AML is an emergent or life-threatening disease, many insurance providers allow patients to come up to a big center to be treated, which I think is more than appropriate. So, we get into details of logistics last, because that’s the one thing that we can often overcome by providing additional resources and support. In terms of patient preference, if that’s what you mean with that, I would say I leave logistics to last, but we always consider and we do our best to accommodate.  

And that might be where we inform them we will look into getting a local partner to help us with additional therapies after the first month or upon discharge. So, it totally depends on the scenario for a patient, whether or not they have a local provider and a local hospital that could accommodate acute leukemia. I always tell patients ideally you don’t want to go to a place that only sees this once per year. You want to go to a place where everyone has seen it multiple times, including the nurses on the floors.  

So, that way, when there’s a complication, everyone knows what to do. We don’t want any “surprises” when it’s really just run-of-the-mill standard stuff for us every day. In terms of what patients desire, we always keep that in the conversation of their level of support. Can they swallow pills? Are they able to cope with being in and out of the hospital? All that stuff gets considered, but I think if they hear about the plan, about what’s required, when my expectation would be for a response, when the frequency of trips to a big city would decrease, how I could get a local partner to help with some of the lab or transfusion burden.  

Many of those preferences that they thought they had diminished, because they recognize that we found a way to make it work.  

Katherine Banwell:

Dr. Garcia, you mentioned earlier the fact that some therapies can cause a lot of side effects, like nausea. And certainly, speaking up and telling your healthcare team how you’re feeling and what some of the symptoms and side effects are, that’s really essential. What is the impetus for someone to consider changing treatment if something is just absolutely not agreeing with them?  

Dr. Jacqueline Garcia:

So, there are many reasons to change a treatment. One is a patient doesn’t tolerate it. It depends on what the issue is. Is it something that’s serious, like a liver or enzyme abnormality that is very abnormal, or a new cardiac problem where it would warrant a change or a dose reduction? That makes sense. There is definitely – often, there’s a lot of guidance in the package inserts or within a clinical trial and how to manage that. But if patient has some intolerabilities that could be overcome with standard supportive care methods, I would make sure we’ve done that.   

So, I would make sure you give you medical team the chance to fix any nausea. We have so many great antinausea drugs. I would want to make sure – or if constipation or diarrhea. It’s often a GI issue that patients get really bothered by.  

I would try to delineate whether or not the side effect was really from the chemo or is from the leukemia that is not yet under control. Or is it another medical condition or a drug-drug interaction that was missed. So, I would do my best to make sure there wasn’t something that was fixable or something else that should be addressed. We otherwise would recommend changing therapy for an extreme intolerability if there was another equivalent better option. And if someone’s disease does not respond to treatment, then we would consider another therapy, too.  

Understanding AML Treatment Categories

 

Understanding AML Treatment Categories from Patient Empowerment Network on Vimeo.

What are the available classes of therapy for acute myeloid leukemia (AML)? Dr. Jacqueline Garcia reviews AML treatment options, ranging from chemotherapy and stem cell transplant to supportive care. 

Dr. Jacqueline Garcia is an oncologist and AML researcher at the Dana-Farber Cancer Institute. Learn more about Dr. Garcia.

See More from Thrive AML

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New and Emerging AML Therapies Being Studied in Clinical Trials

New and Emerging AML Therapies Being Studied in Clinical Trials


Transcript:

Katherine Banwell:

In your experience, what does it mean to thrive with AML?   

Dr. Jacqueline Garcia:

I think that’s a really great question, and I’m glad you’re asking me now as opposed to a decade ago. In the last several years, we’ve had a tremendous number of drugs that got FDA-approved and a lot of exciting clinical trials that have not only shown efficacy and safety but really some long-term responses. So, we can now focus on not just finding what drug can work, which used to be our problem 10 years ago, since we had very limited therapeutic tools, meaning treatments. We now have several treatments available.  

So, when I think of what it means to thrive, it’s identifying the right treatment for each individual patient with acute myeloid leukemia, because what might be recommended for one patient may not be the right for another. And there are many different patient- and disease-related factors that go into that decision-making.  

Katherine Banwell:

Can you walk us through the classes of treatment that are considered when choosing an AML treatment approach?  

Dr. Jacqueline Garcia:

Yeah. In terms of the different classes of treatments, I would say we think of probably three broad categories. One would be – sorry, four broad categories. One would be intensive chemotherapy. And that involves generally hospitalization. Another would be less intensive therapy. That could involve a mixture of inpatient or outpatient therapy. That could also include targeted therapy. The third would be clinical trials, which can include any of the former options I recommended, but they would be in an experimental study. And the fourth would be focusing solely on supportive care or hospice for patients that are too sick to receive therapy.  

Other aspects that are specific, such as pills, versus IV, versus role of transplant, I don’t see it as being separate. You don’t go right to transplant when you have a diagnosis of AML. You have to be in remission. So, transplant, for instance, would come after an intensive therapy or after the less intensive chemotherapy. So, I see that as being the second step once I choose the right treatment option for the patient.  

Katherine Banwell:

And when you’re talking about transplant, you’re talking about stem cell transplant, right?  

Dr. Jacqueline Garcia:

Yes. Stem cell transplant, bone marrow transplant – they mean the same thing. We recruit stem cells from donors that are related or unrelated, and we mobilize them from bone marrow to blood. And so, we can collect stem cells either from blood or bone marrow at this point. So, that’s exactly right.  

Katherine Banwell:

And what about targeted therapy?  

Dr. Jacqueline Garcia:

We have targeted therapy available that’s IV or pill form. And so, any one of these options can be considered. But everything is very patient-specific, and I am very happy to tell you some of the categories and nuances of things that I look at, because I don’t usually just offer patients a menu.  

I tell them what’s appropriate based on their patient characteristics, meaning what their liver function is, their heart function, their history, medical history, what their labs show. And then, I look at their disease history. We are now in an era where we have options. So, I look to see are there mutations that are targetable. Are there not? Are there markers on the surface of their leukemia cells that suggest that there’s a target for an immunotherapy?  

So, we don’t offer classes per se without it being specific. So, I always look to see what are the patient disease-specific characteristics, and then I start the conversation about what the potential options could be and then what I think the best option would be for that particular case.  

How Is Advanced Prostate Cancer Treatment Personalized?

How Is Advanced Prostate Cancer Treatment Personalized? from Patient Empowerment Network on Vimeo.

Tests results, including results of biomarker testing, may help to personalize advanced prostate cancer treatment. Expert Dr. Xin Gao shares an overview of the testing that patients should undergo and how the results are used in determining a treatment plan for optimal care.

Dr. Xin Gao is a Medical Oncologist at Massachusetts General Hospital. Learn more about this expert Dr. Gao.

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Transcript:

Katherine:

I’d like to talk about what goes into deciding on a treatment path. What testing is used to understand a patient’s individual disease?  

Dr. Gao:

There is a lot of testing that we do for – to try and characterize a patient’s individual disease and try to select an optimal management strategy for their specific cancer and their specific situation.  

We look at the biopsy, the pathology. The most common type of prostate cancer is called adenocarcinoma, but rarely we see certain other types under the microscope, things like neuroendocrine or small cell prostate cancers that tend to be treated in a different way. We look at things like the Gleason score.  

That tells us a bit more about sort of the aggressiveness of this cancer, as well as the PSA, you know, it’s a very good correlate for how the cancer is doing in general once somebody has been diagnosed with prostate cancer. For imaging tests, we commonly rely on imaging. We look at prostate MRIs to get an idea of the local extent of the prostate tumor. We get things like bone scans and CAT scans to look at the entire rest of the body to see if or where the cancer may have spread to.  

And there are newer imaging tests like the PSMA PET scan, which we commonly use now, which is a much more sensitive test for detecting prostate cancer in 2023 compared to traditional scans like CAT scans and bone scans. I also commonly make use of genetic testing and molecular information.  

So, for any patient with an advanced prostate cancer, I do recommend both what we call a germline test, which is testing for inherited cancer genes that a patient could have gotten from the parents and pass onto their kids, as well as somatic testing, which is testing the cancer itself to see what genetic mutations or alterations might’ve developed within their cancer. And that can actually factor into certain treatments that the patient may or may not be more likely to benefit from if they have these genetic mutations. 

Katherine:

Dr. Gao, a patient sent in this question prior to the program. What other genetic testing, beside BRCA markers, are important for deciding future targeted therapies and how are each of them used? 

Dr. Gao:

Yeah, that’s a great question. Targeted therapies have been used in a lot of different cancers and it’s only really within the past few years that we’re using them as a standard of care routinely in prostate cancers. So, BRCA2 and BRCA1 mutations are some of the more common mutations or genetic alterations that are targetable in prostate cancer. Recently, there have been multiple FDA approvals of different drugs that are called PARP inhibitor, which are able to target the cancer if they have BRCA1 or BRCA2 mutations.  

Beyond BRCA2 and BRCA1, there’s a panel of what’s called homologous recombination repair genes and that’s defined differently in varying extents, depending on the specific drug. That has been FDA approved, but in general, it’s about 12 to 14 genes total and they actually include the BRCA2 and BRCA1 genes.  

So, some of the ones that have been…it seems like the data shows maybe more activity or better efficacy with these PARP inhibitors include a gene called PALB2, P-A-L-B 2. It’s not a very common mutation that we see, but it is something that we should look for because even if it’s not common overall for the patient who has it, it could be a very helpful and useful gene to know that that they have and it certainly would warrant treatment with a PARP inhibitor. 

The other sort of dozen  or so…10-12 genes in this homologous recombination repair pathway, the data, I would say, is still early and it is still somewhat limited in terms of how much people with those gene mutations truly benefit from these PARP inhibitors, but I do think it’s important to look for them, to know that if they do have one of these genetic mutations that it does make a PARP inhibitor an option for them. And then, beyond these HRR genes, I always look for something called a microsatellite instability or mismatched repair deficiency. These are sort of genetic features or really a panel of about four genes involved in a cellular process called – a DNA repair process called mismatch repair.  

For those patients that have either mismatched repair deficiency or microsatellite instability high cancers, I do recommend that they consider an immunotherapy medication called pembrolizumab which is FDA-approved regardless of cancer type for any MSI high or mismatched repair cancer and they’ve shown pretty solid activity for those kinds of cancers. 

PODCAST: Thriving With AML | Tips and Support for Navigating Treatment

 

How can you navigate care and thrive with acute myeloid leukemia (AML)? In this webinar, Dr. Jacqueline Garcia, an AML specialist and researcher, discusses the treatment and management of AML. Dr. Garcia will review factors that impact therapy choices and shares advice and resources for people living with AML.
 
Dr. Jacqueline Garcia is an oncologist and AML researcher at the Dana-Farber Cancer Institute. Learn more about Dr. Garcia.

Download Resource Guide

See More from Thrive AML

Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for this webinar. Today’s program is about how to live and thrive with AML. We’re going to discuss how to live well with AML and why you should play an active role in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.  

Well, let’s meet our guest today. Joining me is Dr. Jacqueline Garcia. Dr. Garcia, welcome. Would you please introduce yourself?  

Dr. Jacqueline Garcia:

Yes. Hi. My name is Jacqueline Garcia. I’m an oncologist at the Dana-Farber Cancer Institute. I’m a clinical translational investigator. And what this means is I take care of patients with acute and chronic leukemias. I focus mainly on patients with acute myeloid leukemia. The investigator part means, in addition to seeing patients, I spend a lot of time writing, developing, and executing clinical trials in the AML space. We know that there have been so many wonderful therapies that we helped to move froward and bring to the field and so there is more work to be done. So, having active investigations is a key part of this role.  

Katherine Banwell:

Excellent. Well, thank you for taking the time out of your schedule to join us today. We really appreciate it. We start all of our webinars in our Thrive Series with the same question. In your experience, what does it mean to thrive with AML?  

Dr. Jacqueline Garcia:

I think that’s a really great question and I’m glad you’re asking me now as opposed to a decade ago. In the last several years, we’ve had a tremendous number of drugs that got FDA-approved and a lot of exciting clinical trials that have not only shown efficacy and safety but really some long-term responses. So, we can now focus on not just finding what drug can work, which used to be our problem 10 years ago, since we had very limited therapeutic tools, meaning treatments. We now have several treatments available.  

So, when I think of what it means to thrive, it’s identifying the right treatment for each individual patient with acute myeloid leukemia, because what might be recommended for one patient may not be the right for another. And there are many different patient- and disease-related factors that go into that decision-making.  

Katherine Banwell:

Thank you for that, Dr. Garcia. It helps guide us as we move into our conversation. Typically, there are a number of team members to care for a patient. Who is part of an AML healthcare team?  

Dr. Jacqueline Garcia:

Absolutely. We definitely cannot work on our own. Our team is very large, and it’s because these patients require a lot of support. At a bare minimum, a healthcare team will include at least one physician or an oncologist. The AML healthcare team might also include a second oncologist – that could be a bone marrow transplant doctor.  

Other members that are very critical include having a mid-leveler available that’s a physician assistant or a nurse practitioner. Often, an oncologist who runs a busy practice, who takes care of patients that could be very sick, like AML, they work in partnership with often very talented physician assistants and nurse practitioners. I know I do.  

In addition to that, I’m at an academic center so I’m super fortunate. I have really amazing and very smart hematology oncology fellows and residents that also follow to learn how to take care of patients. But we also, in the background, that patients don’t see – we have a pharmacist that helps us with making sure that drugs are prescribed correctly. They often call the patients with oral therapies to follow up. We have financial resource teams to help patients, to link them to LLS for support for bills that might come up, or transportation, or linking them up to other services that could help to defray or reduce costs.  

So, the healthcare team is quite extensive. But in terms of those that are patient-facing, it’s primarily the MDM that are mid-leveler. Some teams operate also with a nurse or a nurse care coordinator. That’s pretty common, too. And that person helps to not only schedule but also to answer pages or phone calls from patients if the medical team is not doing that.  

Katherine Banwell: What about a social worker or psychologist?  

Dr. Jacqueline Garcia:

Oh. Yes. Yes. So, absolutely. So, every patient can be offered, if needed, access to an inpatient or outpatient social worker. Often, if my patients are admitted we have them see a social worker because that’s fairly seamless. Otherwise, for outpatient, if we identify any particular needs or there’s an interest, we’ll link them up with a social worker. This is the same that goes for physical therapy, or nutritionists, or those other ancillary services that can be really critical when patients are getting started.  

Katherine Banwell:

Yeah. Of course, getting appropriate care and treatment is essential to thriving. Can you walk us through the classes of treatment that are considered when choosing an AML treatment approach?  

Dr. Jacqueline Garcia:

Yeah. In terms of the different classes of treatments, I would say we think of probably three broad categories. One would be – sorry, four broad categories. One would be intensive chemotherapy. And that involves generally hospitalization. Another would be less intensive therapy. That could involve a mixture of inpatient or outpatient therapy. That could also include targeted therapy. The third would be clinical trials, which can include any of the former options I recommended, but they would be in an experimental study. And the fourth would be focusing solely on supportive care or hospice for patients that are too sick to receive therapy.  

Other aspects that are specific, such as pills, versus IV, versus role of transplant, I don’t see it as being separate. You don’t go right to transplant when you have a diagnosis of AML. You have to be in remission. So, transplant, for instance, would come after an intensive therapy or after the less intensive chemotherapy. So, I see that as being the second step once I choose the right treatment option for the patient.  

Katherine Banwell:

And when you’re talking about transplant, you’re talking about stem cell transplant, right?  

Dr. Jacqueline Garcia:

Yes. Stem cell transplant, bone marrow transplant – they mean the same thing. We recruit stem cells from donors that are related or unrelated, and we mobilize them from bone marrow to blood. And so, we can collect stem cells either from blood or bone marrow at this point. So, that’s exactly right.  

Katherine Banwell:

And what about targeted therapy?  

Dr. Jacqueline Garcia:

We have targeted therapy available that’s IV or pill form. And so, any one of these options can be considered. But everything is very patient-specific, and I am very happy to tell you some of the categories and nuances of things that I look at, because I don’t usually just offer patients a menu.  

I tell them what’s appropriate based on their patient characteristics, meaning what their liver function is, their heart function, their history, medical history, what their labs show. And then, I look at their disease history. We are now in an era where we have options. So, I look to see are there mutations that are targetable. Are there not? Are there markers on the surface of their leukemia cells that suggest that there’s a target for an immunotherapy?  

So, we don’t offer classes per se without it being specific. So, I always look to see what are the patient disease-specific characteristics, and then I start the conversation about what the potential options could be and then what I think the best option would be for that particular case.  

Katherine Banwell:

As a researcher, Dr. Garcia, you’re on the frontlines of AML treatment. Are there new and emerging therapies that patients should be aware of?  

Dr. Jacqueline Garcia:

Yeah. I think we’re at this really exciting point now where we had for a long time just been giving people standard two agent intensive chemotherapy. We have been studying in Phase II and Phase III settings, and even in Phase I – which means testing safety out for the first time. We’ve been moving a lot of treatments to more mature settings where we’re testing the addition of a third drug. So, for people that are getting intensive chemo, we’re looking at, “Can we add a pill to augment responses deep in them to reduce risk of disease returning?”  

For less intensive chemotherapies, one of the most common regimens we now use is something called azacitidine (Vidaza), which is a hypomethylating agent that is given by IV or subcutaneous administration. Plus, a pill called venetoclax (Venclexta).   

We helped to get that FDA-approved a couple of years ago. That combination of therapy, we call that a doublet, meaning it’s two drugs – because it’s so well-tolerated and active, we’re now asking the greedy question of, “Well, can we make it more active for patients since we’re seeing how well-tolerated it is?”  

So, there have been a lot of therapies that are currently under investigation that are adding a third drug to these less-intensive doublets. So, there’s a lot of therapies under investigation to test, “Can we add an immunotherapy target? Is there another pill that we can add? Is there another targeting mutation to add to the doublet?” So, we’re looking at AML therapies from different angles. We’re looking at adding something to the existing new standard of care – those are these new, so-called, triplets.  

We’re looking at still the role of cellular therapy or CAR Ts targeting leukemia cells from an immunotherapy standpoint.  

That remains underdeveloped overall, and we have not succeeded as well, like our lymphoid colleagues in the lymphoma and acute lymphoblastic leukemia realm where there are drugs that are active and FDA-approved.  

So, we’re still trying to identify the right target. But those are some of the areas that are currently under study.  

Katherine Banwell:

You touched on this earlier, Dr. Garcia, but I’d like to get into a bit more detail. With all the treatment options available, how do you decide who gets what? Tell us what is considered when choosing treatment for a patient.   

Dr. Jacqueline Garcia:

When I – this is a complicated question, because it’s not like you follow any particular algorithm. But when I meet a patient, I make a decision on what’s important to the patient and what’s  their goal. If I know – I need to understand their overall health to get a sense of are there ongoing competing risk factors that are active and more likely to impede with response, ability to deliver chemo, ability to get to transplant, something that tells me that’s not a possibility, or is their age too advanced – meaning greater than 75 – where we know that some of the treatments are not safe to deliver in that setting?  

So, I take a look at a patient’s overall health and age to make a decision. I take a look at bone marrow biopsy and lab findings to understand the flavor of their leukemia, from chromosomes to mutations. And because I am familiar with the data to give me a sense of what’s safe, what’s tolerable, and importantly what types of diseases, or subtypes of AML, would respond to one therapy over another, that’s how I formulate a recommendation.   

And based on all of that, all together, I’ll talk to them about treating the AML in steps. The first step is getting them into a remission, which can be done regardless of therapy type. That means to get their bone marrow under control, blood counts to recover. The second step, which is a more involved conversation that I often give a little bit of a hint of, but I go into greater detail over time, because we will see each other quite a lot, whether in the hospital or in clinic, is how to keep them in remission.   

And that’s where details about things like transplant come into play. I do my best to not overwhelm them, because when a patient hears the word transplant – and that’s often what they hear from family and friends because that’s what you can Google – they don’t know that there are many things, or many weeks of therapy, that have to happen in advance of transplant even being considered or happening. And transplant can’t even happen until someone’s in remission.  

But that is always on the forefront of a leukemia doctor’s mind, “Can I bring this patient to a transplantation? How successful will I be and what else do I need to give them to get them there sooner, safer, with a deeper response?” So, that way transplant could be successful. Transplant, by the way, is when we give a patient someone else’s stem cells that match their HLA typing, or their white blood cell signature.  

And it helps us to use someone else’s immune system to completely irradicate any microscopic leftover leukemia in a patient. But that is only successful when patients have good disease control or remissions. And that is only also successful if we have a donor for the patient, both of which  require at least several weeks to a couple of months of therapy. But that process is always initiated and ongoing in the background. And so, we often do this in piecemeal, because getting a diagnosis is already overwhelming. Learning about treatment is overwhelming.  

Learning about the frequency of labs, transfusions, being hospitalized, and then details about what a transplant would entail can be also overwhelming. But a lot of family and friends like to ask, because they feel like that is one way they might be able to help a patient. So, I know that they often eagerly ask the patient, “Well, what about this? How can I help?”  

Katherine Banwell:

Right. I can imagine that patient preference is also considered. But what kind of questions should patients ask about their treatment regimen?  

Dr. Jacqueline Garcia:

I always tell patients that I care very much about things like travel, hotels, all that jazz. But I always tell them let’s first talk about their health, what treatment I would recommend based on the available options and what their disease would mostly respond to, because I want it to be successful. And I always tell them let’s reserve questions on how it’s going to be done for last. I call that the logistics. I will never bring up or recommend something that could never be possible. But that being said, I try not to let the commute determine the decision.  

Whether or not there needs to be a hospitalization versus a hotel stay. I always consider then the background, but that financial decision should not drive the best treatment choice for a patient. Very fortunately, we’re in a country where patients have the ability – often, not always – to seek second opinions or to travel to academic centers.  

And because AML is an emergent or life-threatening disease, many insurance providers allow patients to come up to a big center to be treated, which I think is more than appropriate. So, we get into details of logistics last, because that’s the one thing that we can often overcome by providing additional resources and support. In terms of patient preference, if that’s what you mean with that, I would say I leave logistics to last, but we always consider and we do our best to accommodate.  

And that might be where we inform them we will look into getting a local partner to help us with additional therapies after the first month or upon discharge. So, it totally depends on the scenario for a patient, whether or not they have a local provider and a local hospital that could accommodate acute leukemia. I always tell patients ideally you don’t want to go to a place that only sees this once per year. You want to go to a place where everyone has seen it multiple times, including the nurses on the floors.  

So, that way, when there’s a complication, everyone knows what to do. We don’t want any “surprises” when it’s really just run-of-the-mill standard stuff for us every day. In terms of what patients desire, we always keep that in the conversation of their level of support. Can they swallow pills? Are they able to cope with being in and out of the hospital? All that stuff gets considered, but I think if they hear about the plan, about what’s required, when my expectation would be for a response, when the frequency of trips to a big city would decrease, how I could get a local partner to help with some of the lab or transfusion burden.  

Many of those preferences that they thought they had diminished, because they recognize that we found a way to make it work.  

Katherine Banwell:

Okay. Well, that’s really good to know. You touched on oral therapies a bit ago, and I know that they’re available for certain patients. Do you have any advice for patients who are in charge now of administering their own therapy?  

Dr. Jacqueline Garcia:

Yeah, I think that taking pills in general is hard for anybody, whether they’re naïve to pills. I definitely have patients that have never been on anything, and suddenly they’re on many medicines, to other people that are managing multiple medical conditions and this is yet another burden to add. I would say having an oral regimen is wonderful. It offers a lot of convenience. But we are all very thoughtful, and we all need to be proactive about looking for drug-drug interactions, because often there could be increases in the chemotherapy presence when another drug is on board.  

Sometimes, antibiotics are added on but they don’t realize it can add to side effects to chemotherapy. So, I would say number one is always make sure your oncology team is aware of the medications you are on or get recommended to add on in the midst of therapy, so we can make sure there are appropriate dosage estimates or if a particular drug should be avoided, then we can do that.  

I would say, too, having oral therapies is great, but there’s also financial toxicity that comes with it. Sometimes copays can get hefty. So, just because it’s oral, it’s not always convenient financially. Also, when things are oral it can add to more GI or mal gut toxicity. So, we’re always keeping in mind how many oral therapies, what drugs they are, so we don’t increase nausea and diarrhea, which can happen frequently when you’re requiring the GI tract to absorb the therapies that are necessary to eliminate the disease.  

So, all these things are under consideration. But to help people that are on oral therapies, it’s helpful to let your providers know if you’re noticing a pattern of nausea, so we can premedicate, have you take a nausea medicine before you take the chemo. You could also put a timer on your phone if you’re not used to taking medicines to serve as a reminder. You could create little calendars or check off on a paper calendar when you’ve taken a drug if you need help with reminding.  

So, there are little tricks like that. I always consider using a pillbox if you don’t have other pills to mix in and if you’re the only one touching it. I don’t want anybody to be exposed to therapies that they shouldn’t be otherwise.  

Katherine Banwell:

That’s good advice. Thank you. If a patient is feeling uncomfortable with the direction of their treatment plan or their care, should they consider a second opinion or even consulting a specialist?  

Dr. Jacqueline Garcia:

Oh, 100 percent. I would say – I think that I’m spoiled. I’m a leukemia specialist, so they’re already seeing a specialist when a patient sees me. I don’t take care of any other cancers. But, I would say, for anyone seeing any oncologist in general, I would – number one, it doesn’t do the medical team any favors if you withhold any feelings of how the treatment’s going. Meaning, if you feel uncomfortable or that you’re having symptoms or people are taking too long to get back to you based on your experience.   

I would just make sure you do your best to at least let them know so that they have the ability to adjust or accommodate whatever need you might have that might be different than what they’re used to, because every patient’s different. Some people have a really great support system. Or they have a little bit of experience of being a patient. Different coping mechanisms. Everyone’s different. There’s no right or wrong. But I would just make sure that it’s clear with your existing team because they’re actively seeing you. Give them a chance to make the experience better.  

I would for sure seek a second opinion. Don’t delay – I will just put this disclaimer. I would not delay treatment for an AML if your current doctor is giving you a good plan and you feel confident that they have looked into whether or not you need to go to a bigger leukemia center and all that other stuff. But if you feel like they are giving you a good plan, don’t delay your therapy in the beginning, because you might get sick.  

If, however, there is demonstration of safety and time to see someone within a short timeframe for a second opinion at the time of diagnosis before treatment started, then that’s okay. But wouldn’t wait a few months to go looking around, because that could put your health at risk. Once you’re on treatment, seeking a second opinion, if you’re dissatisfied with your ongoing team, it’s fine. I always want patients to feel comfortable with their treatment plan.  

But I would recognize that you want to make it clear to your current team that they’re still helping you and responsible for your treatment. Because if you, for instance, started seeing multiple doctors and they won’t know who should be helping to follow up on certain things, who’s going to be scheduling the next round of therapy. And that ends up putting more ownership unnecessarily onto the patient where they might not have needed to have all that extra responsibility. So, I would just say just make sure that’s clear. Yeah.  

Katherine Banwell:

Dr. Garcia, you mentioned earlier the fact that some therapies can cause a lot of side effects, like nausea. And certainly, speaking up and telling your healthcare team how you’re feeling and what some of the symptoms and side effects are, that’s really essential. What is the impetus for someone to consider changing treatment if something is just absolutely not agreeing with them?  

Dr. Jacqueline Garcia:

So, there are many reasons to change a treatment. One is a patient doesn’t tolerate it. It depends on what the issue is. Is it something that’s serious, like a liver or enzyme abnormality that is very abnormal, or a new cardiac problem where it would warrant a change or a dose reduction? That makes sense. There is definitely – often, there’s a lot of guidance in the package inserts or within a clinical trial and how to manage that. But if patient has some intolerabilities that could be overcome with standard supportive care methods, I would make sure we’ve done that.  

So, I would make sure you give you medical team the chance to fix any nausea. We have so many great antinausea drugs. I would want to make sure – or if constipation or diarrhea. It’s often a GI issue that patients get really bothered by.  

I would try to delineate whether or not the side effect was really from the chemo or is from the leukemia that is not yet under control. Or is it another medical condition or a drug-drug interaction that was missed. So, I would do my best to make sure there wasn’t something that was fixable or something else that should be addressed. We otherwise would recommend changing therapy for an extreme intolerability if there was another equivalent better option. And if someone’s disease does not respond to treatment, then we would consider another therapy, too.  

Katherine Banwell:

Dr. Garcia, I want to make sure that we get to some of the audience questions that were sent to us prior to this program. Let’s start with this one.  

 Jerry had this question. “How long can patients stay on azacitidine and venetoclax before relapse or toxicities force them to abandon treatment?”  

Dr. Jacqueline Garcia:

So, this is a good question. I would say azacitidine and venetoclax just got FDA-approved just shy of five years now, and it’s totally changed our treatment paradigm in many great ways. It was initially approved for patients that could not get intensive chemotherapies or were above 75. We call these our older patients, our more vulnerable.  

And we demonstrated and compared to azacitidine alone. It was given with placebo. We saw that the combination of azacitidine and venetoclax not only was safe, well-tolerated, it led to two-and-a-half times higher complete remission rates and impressively longer survival. That’s all we care about, patients are living longer. So, one of the things that we are appreciating in 2023 now, now that we have more patients on azacitidine and venetoclax, is that we have many patients that are long-term responders.  

So, in the original clinical trial we’ve been reported – and we just submitted the update for the long-term follow-up that we presented at the American Society of Hematology meeting in 2022, in December.  

We presented the long-term follow-up data that shows that responses can be durable and even as long as two years or three years in some patients. The average amount of time the patients are on therapy is somewhere between one-and-a-half to two years. But not every patient performs like an average patient.  

We have some that respond for less time. We have some that respond for a longer time. So, I definitely have a few patients that have been on combination therapy, and we’ve gone to year three, then four, and two that got to year five. And that was using the original indication of older the 75, no intensive chemotherapy. Most of those patients in the original trial and led to the approval were not transplant candidates. But once those drugs got approved, more patients that were older started getting this therapy.  

And so, the durability of this treatment might be longer for people that don’t have competing health problems and for specific mutation subtypes. There are a couple of mutation subtypes that include IDH2 and NPM1, where we’ve seen some extreme long-term responders.   

And then, there are others that are much shorter. So, I would say it’s very individual. In terms of toxicities in general, the regimens very well-tolerated. And if it’s not, often it’s because there should be supportive care, prophylaxis, and adjustments to the dosing strategy, which has been well-published. Sometimes, if you have a treating oncologist that is less familiar, they won’t know the nuances of how to adjust the doses, so I would ask your local oncologist to reach out to anybody that was part of the original trials. Often, a lot of us are very responsive to helping out our colleagues to help patients to stay on treatment.  

But at the end of the day, if a patient loses response or has a bad toxicity that makes it very difficult, we have to move on to another therapy.  

Katherine Banwell:

Of course. Carrie sent in this question. “What percent of patients relapse and what percent of patients relapse more than once?”  

Dr. Jacqueline Garcia:

Okay. So, this is a question that I can certainly answer, but I would say it depends on the context. So, if I was taking – any time a patient asks me that, I always ask them what they want to know and what they don’t want to hear, because sometimes hearing numbers can be really daunting to patients overall.  

So, a very large number of patients with leukemia can go on to relapse, which is why, if you’re on a treatment like azacitidine and venetoclax, we continue it every month as long as we can with dose reductions to help with tolerability.  

And that’s why, if you got that regimen or intensive chemo or another clinical trial and you get into remission, we ask the question of can we transplant this patient to do our best to cure them long-term to avoid and reduce the chance of a relapse. So, even with transplant, which remains our gold standard for long-term curability – it’s the only treatment we have that has a guaranteed track record of cure – not every patient that goes to transplant will remain in remission.  

If I were to be asked, “Well, how many relapse,” I would say it depends. I would say if I took the average patient, maybe 40 to 50 percent will relapse. But if you ask me for certain mutation types it could be 90 percent are cured or only 20 percent are cured. So, it’s very individual. It depends on age. It depends on mutations. It depends on the level of response they had before they go to transplant.  

So, I would say even though the word relapse is very scary or disease coming back is definitely a scary thing, there are a lot of people, including me, that are working on ways to reduce risk of relapse, improve how we transplant, improve the treatments around and after transplant, and improving frontline and relapse therapies.  

I think you had a second question of what happens if you relapse once and then what about if relapse happens again? I would say that getting into remission the first time is always the easiest. The way I always think about it is, you kill off all the bad cells that are the easiest to die the first time around with chemotherapy. Anything that’s left behind are often the resistant types. And so, getting into a second remission or responding the second time around with treatment is doable, but it’s much harder.  

So, I would say the majority of patients that relapse the first time will relapse the second time, unless we can successfully bridge them to a transplantation.  

Katherine Banwell:

Yeah. Dr. Garcia, as we close out this conversation, I wanted to get your thoughts on where we stand with progress in helping people live longer and thrive with AML. What would you like to leave the audience with?  

Dr. Jacqueline Garcia:

I think that this is – I feel very lucky with when I entered the field, that in this last decade, as I’ve developed – my time at Dana-Farber, for instance – I’ve seen that there have been so many drugs that we helped to get approved that are now in the hands of local oncologists and other academic oncologists, suggesting that the clinical trials are a gateway to improving treatments and offering new options.  

 We’ve gotten better at understanding what mutations and chromosomes means and personalizing medicines, and that has allowed us to develop smarter and better clinical trials, which we hope we will get to keep approving and making more available to patients. So, I think that this is a really good time for AML, meaning we have more than one option, that is for sure. We can now think about what the patient wants, what the patient, and what their patient disease has in order to make a decision. We weren’t able to do that before.  

So, we can really involve patients so they understand why we would recommend one option versus another. And we are still not done with investigation, even though many drugs got approved in the last five years. There’s a lot more progress to be made, especially in areas that we touched upon, from approving getting patients to transplant, reducing relapse risk, keeping people in remission. Those are all things that I’m personally working on in the clinical trial space and things a lot of my colleagues in the world are working on, too.  

It’s very important to all of us. So, I would say be hopeful that we are not done. There’s a lot of great options out there. We really can personalize. There are a lot of options out there, but everyone will get offered their best therapy and the first-line therapy is the most important. And I am very hopeful that we will keep getting better at prolonging remissions and durability of those responses.   

Katherine Banwell:

Dr. Garcia, thank you so much for taking the time to join us today. It’s been a pleasure.  

Dr. Jacqueline Garcia:

Thank you.  

Katherine Banwell:

And thank you to all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.   

Thriving With AML | Tips and Support for Navigating Treatment

How can you navigate care and thrive with acute myeloid leukemia (AML)? In this webinar, Dr. Jacqueline Garcia, an AML specialist and researcher, discusses the treatment and management of AML. Dr. Garcia will review factors that impact therapy choices and shares advice and resources for people living with AML.
 
Dr. Jacqueline Garcia is an oncologist and AML researcher at the Dana-Farber Cancer Institute. Learn more about Dr. Garcia.

Download Resource Guide

See More from Thrive AML

Related Resources:

How Can You Thrive With AML Advice for Navigating Care.

How Can You Thrive with AML? Advice for Navigating Care

The Benefits of Being Pro-Active in Your AML Care

What Are the Phases of AML Therapy


Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for this webinar. Today’s program is about how to live and thrive with AML. We’re going to discuss how to live well with AML and why you should play an active role in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.  

Well, let’s meet our guest today. Joining me is Dr. Jacqueline Garcia. Dr. Garcia, welcome. Would you please introduce yourself?  

Dr. Jacqueline Garcia:

Yes. Hi. My name is Jacqueline Garcia. I’m an oncologist at the Dana-Farber Cancer Institute. I’m a clinical translational investigator. And what this means is I take care of patients with acute and chronic leukemias. I focus mainly on patients with acute myeloid leukemia. The investigator part means, in addition to seeing patients, I spend a lot of time writing, developing, and executing clinical trials in the AML space. We know that there have been so many wonderful therapies that we helped to move froward and bring to the field and so there is more work to be done. So, having active investigations is a key part of this role.  

Katherine Banwell:

Excellent. Well, thank you for taking the time out of your schedule to join us today. We really appreciate it. We start all of our webinars in our Thrive Series with the same question. In your experience, what does it mean to thrive with AML?  

Dr. Jacqueline Garcia:

I think that’s a really great question and I’m glad you’re asking me now as opposed to a decade ago. In the last several years, we’ve had a tremendous number of drugs that got FDA-approved and a lot of exciting clinical trials that have not only shown efficacy and safety but really some long-term responses. So, we can now focus on not just finding what drug can work, which used to be our problem 10 years ago, since we had very limited therapeutic tools, meaning treatments. We now have several treatments available.  

So, when I think of what it means to thrive, it’s identifying the right treatment for each individual patient with acute myeloid leukemia, because what might be recommended for one patient may not be the right for another. And there are many different patient- and disease-related factors that go into that decision-making.  

Katherine Banwell:

Thank you for that, Dr. Garcia. It helps guide us as we move into our conversation. Typically, there are a number of team members to care for a patient. Who is part of an AML healthcare team?  

Dr. Jacqueline Garcia:

Absolutely. We definitely cannot work on our own. Our team is very large, and it’s because these patients require a lot of support. At a bare minimum, a healthcare team will include at least one physician or an oncologist. The AML healthcare team might also include a second oncologist – that could be a bone marrow transplant doctor.  

Other members that are very critical include having a mid-leveler available that’s a physician assistant or a nurse practitioner. Often, an oncologist who runs a busy practice, who takes care of patients that could be very sick, like AML, they work in partnership with often very talented physician assistants and nurse practitioners. I know I do.  

In addition to that, I’m at an academic center so I’m super fortunate. I have really amazing and very smart hematology oncology fellows and residents that also follow to learn how to take care of patients. But we also, in the background, that patients don’t see – we have a pharmacist that helps us with making sure that drugs are prescribed correctly. They often call the patients with oral therapies to follow up. We have financial resource teams to help patients, to link them to LLS for support for bills that might come up, or transportation, or linking them up to other services that could help to defray or reduce costs.  

So, the healthcare team is quite extensive. But in terms of those that are patient-facing, it’s primarily the MDM that are mid-leveler. Some teams operate also with a nurse or a nurse care coordinator. That’s pretty common, too. And that person helps to not only schedule but also to answer pages or phone calls from patients if the medical team is not doing that.  

Katherine Banwell: What about a social worker or psychologist?  

Dr. Jacqueline Garcia:

Oh. Yes. Yes. So, absolutely. So, every patient can be offered, if needed, access to an inpatient or outpatient social worker. Often, if my patients are admitted we have them see a social worker because that’s fairly seamless. Otherwise, for outpatient, if we identify any particular needs or there’s an interest, we’ll link them up with a social worker. This is the same that goes for physical therapy, or nutritionists, or those other ancillary services that can be really critical when patients are getting started.  

Katherine Banwell:

Yeah. Of course, getting appropriate care and treatment is essential to thriving. Can you walk us through the classes of treatment that are considered when choosing an AML treatment approach?  

Dr. Jacqueline Garcia:

Yeah. In terms of the different classes of treatments, I would say we think of probably three broad categories. One would be – sorry, four broad categories. One would be intensive chemotherapy. And that involves generally hospitalization. Another would be less intensive therapy. That could involve a mixture of inpatient or outpatient therapy. That could also include targeted therapy. The third would be clinical trials, which can include any of the former options I recommended, but they would be in an experimental study. And the fourth would be focusing solely on supportive care or hospice for patients that are too sick to receive therapy.  

Other aspects that are specific, such as pills, versus IV, versus role of transplant, I don’t see it as being separate. You don’t go right to transplant when you have a diagnosis of AML. You have to be in remission. So, transplant, for instance, would come after an intensive therapy or after the less intensive chemotherapy. So, I see that as being the second step once I choose the right treatment option for the patient.  

Katherine Banwell:

And when you’re talking about transplant, you’re talking about stem cell transplant, right?  

Dr. Jacqueline Garcia:

Yes. Stem cell transplant, bone marrow transplant – they mean the same thing. We recruit stem cells from donors that are related or unrelated, and we mobilize them from bone marrow to blood. And so, we can collect stem cells either from blood or bone marrow at this point. So, that’s exactly right.  

Katherine Banwell:

And what about targeted therapy?  

Dr. Jacqueline Garcia:

We have targeted therapy available that’s IV or pill form. And so, any one of these options can be considered. But everything is very patient-specific, and I am very happy to tell you some of the categories and nuances of things that I look at, because I don’t usually just offer patients a menu.  

I tell them what’s appropriate based on their patient characteristics, meaning what their liver function is, their heart function, their history, medical history, what their labs show. And then, I look at their disease history. We are now in an era where we have options. So, I look to see are there mutations that are targetable. Are there not? Are there markers on the surface of their leukemia cells that suggest that there’s a target for an immunotherapy?  

So, we don’t offer classes per se without it being specific. So, I always look to see what are the patient disease-specific characteristics, and then I start the conversation about what the potential options could be and then what I think the best option would be for that particular case.  

Katherine Banwell:

As a researcher, Dr. Garcia, you’re on the frontlines of AML treatment. Are there new and emerging therapies that patients should be aware of?  

Dr. Jacqueline Garcia:

Yeah. I think we’re at this really exciting point now where we had for a long time just been giving people standard two agent intensive chemotherapy. We have been studying in Phase II and Phase III settings, and even in Phase I – which means testing safety out for the first time. We’ve been moving a lot of treatments to more mature settings where we’re testing the addition of a third drug. So, for people that are getting intensive chemo, we’re looking at, “Can we add a pill to augment responses deep in them to reduce risk of disease returning?”  

For less intensive chemotherapies, one of the most common regimens we now use is something called azacitidine (Vidaza), which is a hypomethylating agent that is given by IV or subcutaneous administration. Plus, a pill called venetoclax (Venclexta).   

We helped to get that FDA-approved a couple of years ago. That combination of therapy, we call that a doublet, meaning it’s two drugs – because it’s so well-tolerated and active, we’re now asking the greedy question of, “Well, can we make it more active for patients since we’re seeing how well-tolerated it is?”  

So, there have been a lot of therapies that are currently under investigation that are adding a third drug to these less-intensive doublets. So, there’s a lot of therapies under investigation to test, “Can we add an immunotherapy target? Is there another pill that we can add? Is there another targeting mutation to add to the doublet?” So, we’re looking at AML therapies from different angles. We’re looking at adding something to the existing new standard of care – those are these new, so-called, triplets.  

We’re looking at still the role of cellular therapy or CAR Ts targeting leukemia cells from an immunotherapy standpoint.  

That remains underdeveloped overall, and we have not succeeded as well, like our lymphoid colleagues in the lymphoma and acute lymphoblastic leukemia realm where there are drugs that are active and FDA-approved.  

So, we’re still trying to identify the right target. But those are some of the areas that are currently under study.  

Katherine Banwell:

You touched on this earlier, Dr. Garcia, but I’d like to get into a bit more detail. With all the treatment options available, how do you decide who gets what? Tell us what is considered when choosing treatment for a patient.   

Dr. Jacqueline Garcia:

When I – this is a complicated question, because it’s not like you follow any particular algorithm. But when I meet a patient, I make a decision on what’s important to the patient and what’s  their goal. If I know – I need to understand their overall health to get a sense of are there ongoing competing risk factors that are active and more likely to impede with response, ability to deliver chemo, ability to get to transplant, something that tells me that’s not a possibility, or is their age too advanced – meaning greater than 75 – where we know that some of the treatments are not safe to deliver in that setting?  

So, I take a look at a patient’s overall health and age to make a decision. I take a look at bone marrow biopsy and lab findings to understand the flavor of their leukemia, from chromosomes to mutations. And because I am familiar with the data to give me a sense of what’s safe, what’s tolerable, and importantly what types of diseases, or subtypes of AML, would respond to one therapy over another, that’s how I formulate a recommendation.   

And based on all of that, all together, I’ll talk to them about treating the AML in steps. The first step is getting them into a remission, which can be done regardless of therapy type. That means to get their bone marrow under control, blood counts to recover. The second step, which is a more involved conversation that I often give a little bit of a hint of, but I go into greater detail over time, because we will see each other quite a lot, whether in the hospital or in clinic, is how to keep them in remission.   

And that’s where details about things like transplant come into play. I do my best to not overwhelm them, because when a patient hears the word transplant – and that’s often what they hear from family and friends because that’s what you can Google – they don’t know that there are many things, or many weeks of therapy, that have to happen in advance of transplant even being considered or happening. And transplant can’t even happen until someone’s in remission.  

But that is always on the forefront of a leukemia doctor’s mind, “Can I bring this patient to a transplantation? How successful will I be and what else do I need to give them to get them there sooner, safer, with a deeper response?” So, that way transplant could be successful. Transplant, by the way, is when we give a patient someone else’s stem cells that match their HLA typing, or their white blood cell signature.  

And it helps us to use someone else’s immune system to completely irradicate any microscopic leftover leukemia in a patient. But that is only successful when patients have good disease control or remissions. And that is only also successful if we have a donor for the patient, both of which  require at least several weeks to a couple of months of therapy. But that process is always initiated and ongoing in the background. And so, we often do this in piecemeal, because getting a diagnosis is already overwhelming. Learning about treatment is overwhelming.  

Learning about the frequency of labs, transfusions, being hospitalized, and then details about what a transplant would entail can be also overwhelming. But a lot of family and friends like to ask, because they feel like that is one way they might be able to help a patient. So, I know that they often eagerly ask the patient, “Well, what about this? How can I help?”  

Katherine Banwell:

Right. I can imagine that patient preference is also considered. But what kind of questions should patients ask about their treatment regimen?  

Dr. Jacqueline Garcia:

I always tell patients that I care very much about things like travel, hotels, all that jazz. But I always tell them let’s first talk about their health, what treatment I would recommend based on the available options and what their disease would mostly respond to, because I want it to be successful. And I always tell them let’s reserve questions on how it’s going to be done for last. I call that the logistics. I will never bring up or recommend something that could never be possible. But that being said, I try not to let the commute determine the decision.  

Whether or not there needs to be a hospitalization versus a hotel stay. I always consider then the background, but that financial decision should not drive the best treatment choice for a patient. Very fortunately, we’re in a country where patients have the ability – often, not always – to seek second opinions or to travel to academic centers.  

And because AML is an emergent or life-threatening disease, many insurance providers allow patients to come up to a big center to be treated, which I think is more than appropriate. So, we get into details of logistics last, because that’s the one thing that we can often overcome by providing additional resources and support. In terms of patient preference, if that’s what you mean with that, I would say I leave logistics to last, but we always consider and we do our best to accommodate.  

And that might be where we inform them we will look into getting a local partner to help us with additional therapies after the first month or upon discharge. So, it totally depends on the scenario for a patient, whether or not they have a local provider and a local hospital that could accommodate acute leukemia. I always tell patients ideally you don’t want to go to a place that only sees this once per year. You want to go to a place where everyone has seen it multiple times, including the nurses on the floors.  

So, that way, when there’s a complication, everyone knows what to do. We don’t want any “surprises” when it’s really just run-of-the-mill standard stuff for us every day. In terms of what patients desire, we always keep that in the conversation of their level of support. Can they swallow pills? Are they able to cope with being in and out of the hospital? All that stuff gets considered, but I think if they hear about the plan, about what’s required, when my expectation would be for a response, when the frequency of trips to a big city would decrease, how I could get a local partner to help with some of the lab or transfusion burden.  

Many of those preferences that they thought they had diminished, because they recognize that we found a way to make it work.  

Katherine Banwell:

Okay. Well, that’s really good to know. You touched on oral therapies a bit ago, and I know that they’re available for certain patients. Do you have any advice for patients who are in charge now of administering their own therapy?  

Dr. Jacqueline Garcia:

Yeah, I think that taking pills in general is hard for anybody, whether they’re naïve to pills. I definitely have patients that have never been on anything, and suddenly they’re on many medicines, to other people that are managing multiple medical conditions and this is yet another burden to add. I would say having an oral regimen is wonderful. It offers a lot of convenience. But we are all very thoughtful, and we all need to be proactive about looking for drug-drug interactions, because often there could be increases in the chemotherapy presence when another drug is on board.  

Sometimes, antibiotics are added on but they don’t realize it can add to side effects to chemotherapy. So, I would say number one is always make sure your oncology team is aware of the medications you are on or get recommended to add on in the midst of therapy, so we can make sure there are appropriate dosage estimates or if a particular drug should be avoided, then we can do that.  

I would say, too, having oral therapies is great, but there’s also financial toxicity that comes with it. Sometimes copays can get hefty. So, just because it’s oral, it’s not always convenient financially. Also, when things are oral it can add to more GI or mal gut toxicity. So, we’re always keeping in mind how many oral therapies, what drugs they are, so we don’t increase nausea and diarrhea, which can happen frequently when you’re requiring the GI tract to absorb the therapies that are necessary to eliminate the disease.  

So, all these things are under consideration. But to help people that are on oral therapies, it’s helpful to let your providers know if you’re noticing a pattern of nausea, so we can premedicate, have you take a nausea medicine before you take the chemo. You could also put a timer on your phone if you’re not used to taking medicines to serve as a reminder. You could create little calendars or check off on a paper calendar when you’ve taken a drug if you need help with reminding.  

So, there are little tricks like that. I always consider using a pillbox if you don’t have other pills to mix in and if you’re the only one touching it. I don’t want anybody to be exposed to therapies that they shouldn’t be otherwise.  

Katherine Banwell:

That’s good advice. Thank you. If a patient is feeling uncomfortable with the direction of their treatment plan or their care, should they consider a second opinion or even consulting a specialist?  

Dr. Jacqueline Garcia:

Oh, 100 percent. I would say – I think that I’m spoiled. I’m a leukemia specialist, so they’re already seeing a specialist when a patient sees me. I don’t take care of any other cancers. But, I would say, for anyone seeing any oncologist in general, I would – number one, it doesn’t do the medical team any favors if you withhold any feelings of how the treatment’s going. Meaning, if you feel uncomfortable or that you’re having symptoms or people are taking too long to get back to you based on your experience.   

I would just make sure you do your best to at least let them know so that they have the ability to adjust or accommodate whatever need you might have that might be different than what they’re used to, because every patient’s different. Some people have a really great support system. Or they have a little bit of experience of being a patient. Different coping mechanisms. Everyone’s different. There’s no right or wrong. But I would just make sure that it’s clear with your existing team because they’re actively seeing you. Give them a chance to make the experience better.  

I would for sure seek a second opinion. Don’t delay – I will just put this disclaimer. I would not delay treatment for an AML if your current doctor is giving you a good plan and you feel confident that they have looked into whether or not you need to go to a bigger leukemia center and all that other stuff. But if you feel like they are giving you a good plan, don’t delay your therapy in the beginning, because you might get sick.  

If, however, there is demonstration of safety and time to see someone within a short timeframe for a second opinion at the time of diagnosis before treatment started, then that’s okay. But wouldn’t wait a few months to go looking around, because that could put your health at risk. Once you’re on treatment, seeking a second opinion, if you’re dissatisfied with your ongoing team, it’s fine. I always want patients to feel comfortable with their treatment plan.  

But I would recognize that you want to make it clear to your current team that they’re still helping you and responsible for your treatment. Because if you, for instance, started seeing multiple doctors and they won’t know who should be helping to follow up on certain things, who’s going to be scheduling the next round of therapy. And that ends up putting more ownership unnecessarily onto the patient where they might not have needed to have all that extra responsibility. So, I would just say just make sure that’s clear. Yeah.  

Katherine Banwell:

Dr. Garcia, you mentioned earlier the fact that some therapies can cause a lot of side effects, like nausea. And certainly, speaking up and telling your healthcare team how you’re feeling and what some of the symptoms and side effects are, that’s really essential. What is the impetus for someone to consider changing treatment if something is just absolutely not agreeing with them?  

Dr. Jacqueline Garcia:

So, there are many reasons to change a treatment. One is a patient doesn’t tolerate it. It depends on what the issue is. Is it something that’s serious, like a liver or enzyme abnormality that is very abnormal, or a new cardiac problem where it would warrant a change or a dose reduction? That makes sense. There is definitely – often, there’s a lot of guidance in the package inserts or within a clinical trial and how to manage that. But if patient has some intolerabilities that could be overcome with standard supportive care methods, I would make sure we’ve done that.  

So, I would make sure you give you medical team the chance to fix any nausea. We have so many great antinausea drugs. I would want to make sure – or if constipation or diarrhea. It’s often a GI issue that patients get really bothered by.  

I would try to delineate whether or not the side effect was really from the chemo or is from the leukemia that is not yet under control. Or is it another medical condition or a drug-drug interaction that was missed. So, I would do my best to make sure there wasn’t something that was fixable or something else that should be addressed. We otherwise would recommend changing therapy for an extreme intolerability if there was another equivalent better option. And if someone’s disease does not respond to treatment, then we would consider another therapy, too.  

Katherine Banwell:

Dr. Garcia, I want to make sure that we get to some of the audience questions that were sent to us prior to this program. Let’s start with this one.  

 Jerry had this question. “How long can patients stay on azacitidine and venetoclax before relapse or toxicities force them to abandon treatment?”  

Dr. Jacqueline Garcia:

So, this is a good question. I would say azacitidine and venetoclax just got FDA-approved just shy of five years now, and it’s totally changed our treatment paradigm in many great ways. It was initially approved for patients that could not get intensive chemotherapies or were above 75. We call these our older patients, our more vulnerable.  

And we demonstrated and compared to azacitidine alone. It was given with placebo. We saw that the combination of azacitidine and venetoclax not only was safe, well-tolerated, it led to two-and-a-half times higher complete remission rates and impressively longer survival. That’s all we care about, patients are living longer. So, one of the things that we are appreciating in 2023 now, now that we have more patients on azacitidine and venetoclax, is that we have many patients that are long-term responders.  

So, in the original clinical trial we’ve been reported – and we just submitted the update for the long-term follow-up that we presented at the American Society of Hematology meeting in 2022, in December.  

We presented the long-term follow-up data that shows that responses can be durable and even as long as two years or three years in some patients. The average amount of time the patients are on therapy is somewhere between one-and-a-half to two years. But not every patient performs like an average patient.  

We have some that respond for less time. We have some that respond for a longer time. So, I definitely have a few patients that have been on combination therapy, and we’ve gone to year three, then four, and two that got to year five. And that was using the original indication of older the 75, no intensive chemotherapy. Most of those patients in the original trial and led to the approval were not transplant candidates. But once those drugs got approved, more patients that were older started getting this therapy.  

And so, the durability of this treatment might be longer for people that don’t have competing health problems and for specific mutation subtypes. There are a couple of mutation subtypes that include IDH2 and NPM1, where we’ve seen some extreme long-term responders.   

And then, there are others that are much shorter. So, I would say it’s very individual. In terms of toxicities in general, the regimens very well-tolerated. And if it’s not, often it’s because there should be supportive care, prophylaxis, and adjustments to the dosing strategy, which has been well-published. Sometimes, if you have a treating oncologist that is less familiar, they won’t know the nuances of how to adjust the doses, so I would ask your local oncologist to reach out to anybody that was part of the original trials. Often, a lot of us are very responsive to helping out our colleagues to help patients to stay on treatment.  

But at the end of the day, if a patient loses response or has a bad toxicity that makes it very difficult, we have to move on to another therapy.  

Katherine Banwell:

Of course. Carrie sent in this question. “What percent of patients relapse and what percent of patients relapse more than once?”  

Dr. Jacqueline Garcia:

Okay. So, this is a question that I can certainly answer, but I would say it depends on the context. So, if I was taking – any time a patient asks me that, I always ask them what they want to know and what they don’t want to hear, because sometimes hearing numbers can be really daunting to patients overall.  

So, a very large number of patients with leukemia can go on to relapse, which is why, if you’re on a treatment like azacitidine and venetoclax, we continue it every month as long as we can with dose reductions to help with tolerability.  

And that’s why, if you got that regimen or intensive chemo or another clinical trial and you get into remission, we ask the question of can we transplant this patient to do our best to cure them long-term to avoid and reduce the chance of a relapse. So, even with transplant, which remains our gold standard for long-term curability – it’s the only treatment we have that has a guaranteed track record of cure – not every patient that goes to transplant will remain in remission.  

If I were to be asked, “Well, how many relapse,” I would say it depends. I would say if I took the average patient, maybe 40 to 50 percent will relapse. But if you ask me for certain mutation types it could be 90 percent are cured or only 20 percent are cured. So, it’s very individual. It depends on age. It depends on mutations. It depends on the level of response they had before they go to transplant.  

So, I would say even though the word relapse is very scary or disease coming back is definitely a scary thing, there are a lot of people, including me, that are working on ways to reduce risk of relapse, improve how we transplant, improve the treatments around and after transplant, and improving frontline and relapse therapies.  

I think you had a second question of what happens if you relapse once and then what about if relapse happens again? I would say that getting into remission the first time is always the easiest. The way I always think about it is, you kill off all the bad cells that are the easiest to die the first time around with chemotherapy. Anything that’s left behind are often the resistant types. And so, getting into a second remission or responding the second time around with treatment is doable, but it’s much harder.  

So, I would say the majority of patients that relapse the first time will relapse the second time, unless we can successfully bridge them to a transplantation.  

Katherine Banwell:

Yeah. Dr. Garcia, as we close out this conversation, I wanted to get your thoughts on where we stand with progress in helping people live longer and thrive with AML. What would you like to leave the audience with?  

Dr. Jacqueline Garcia:

I think that this is – I feel very lucky with when I entered the field, that in this last decade, as I’ve developed – my time at Dana-Farber, for instance – I’ve seen that there have been so many drugs that we helped to get approved that are now in the hands of local oncologists and other academic oncologists, suggesting that the clinical trials are a gateway to improving treatments and offering new options.  

 We’ve gotten better at understanding what mutations and chromosomes means and personalizing medicines, and that has allowed us to develop smarter and better clinical trials, which we hope we will get to keep approving and making more available to patients. So, I think that this is a really good time for AML, meaning we have more than one option, that is for sure. We can now think about what the patient wants, what the patient, and what their patient disease has in order to make a decision. We weren’t able to do that before.  

So, we can really involve patients so they understand why we would recommend one option versus another. And we are still not done with investigation, even though many drugs got approved in the last five years. There’s a lot more progress to be made, especially in areas that we touched upon, from approving getting patients to transplant, reducing relapse risk, keeping people in remission. Those are all things that I’m personally working on in the clinical trial space and things a lot of my colleagues in the world are working on, too.  

It’s very important to all of us. So, I would say be hopeful that we are not done. There’s a lot of great options out there. We really can personalize. There are a lot of options out there, but everyone will get offered their best therapy and the first-line therapy is the most important. And I am very hopeful that we will keep getting better at prolonging remissions and durability of those responses.   

Katherine Banwell:

Dr. Garcia, thank you so much for taking the time to join us today. It’s been a pleasure.  

Dr. Jacqueline Garcia:

Thank you.  

Katherine Banwell:

And thank you to all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.   

PODCAST: Advanced Prostate Cancer: How to Access the Best Care and Treatment for YOU

 

Progress in advanced prostate cancer has led to more personalized treatment options and individualized care for people with this diagnosis. Dr. Xin Gao discusses how the results of essential testing can help guide a patient’s prognosis and treatment path, reviews available therapies, and shares advice for self-advocacy.

Bio:
Dr. Xin Gao is a Medical Oncologist at Massachusetts General Hospital. Learn more about Dr. Gao.

Download Resource Guide

See More From INSIST! Prostate Cancer

Transcript:

Katherine:

Hello and welcome. I’m your host Katherine Banwell. Today’s program focuses on how people with advanced prostate cancer can access the best treatment in care. We’ll review essential testing, discuss the latest research, and share tips for self-advocacy. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to a resource guide. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars.  

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Xin Gao. Dr. Gao, welcome. Would you please introduce yourself? 

Dr. Gao:

Yeah. Thank you very much for having me. My name is Xin Gao. I’m a medical oncologist at Mass General Cancer Center in Boston, Massachusetts. I focus on prostate cancer and other cancers involving the urinary system. I’m also involved in our clinical trials program where we’re studying newer and what we hope are better treatments for these types of cancers.  

Katherine:

Well, thank you so much for joining us today. I know you’re a busy guy.  

Dr. Gao:

I’m happy to be here.  

Katherine:

Good. Dr. Gao, this program is focusing on advanced prostate cancer. Would you walk us through how the disease progresses in each stage? 

Dr. Gao:

Sure. I think advanced prostate cancer can mean a lot of different things, but in general, it means a prostate cancer that has either spread out from the prostate gland itself to other areas of the body or has recurred despite either surgery or radiation-based therapy to the primary prostate tumor. 

In each of these situations, typically the focus would on medication types of treatments and we think about advanced prostate cancer as either hormone-sensitive or hormone-resistant, or the other term in the field for it would be castration-resistant, meaning that the prostate cancer is either sensitive to hormonal therapies or perhaps it’s no longer sensitive to the most common type of hormone therapy called androgen deprivation therapy. So, those are sort of the ways that the cancer can progress, and typically all these cancers start as hormone-sensitive prostate cancers and over time, they may evolve and become resistant and become what we call castration-resistant prostate cancer. 

Katherine:

Okay. So, they’re not numbered as in a lot of other cancers, like stage I, stage II?  

Dr. Gao:

Meaning by stage, oh. So, there are stages. All advanced prostate cancers are by definition stage IV. All advanced cancers, in general, are stage IV but advanced prostate cancer would be stage IV. Most prostate cancers actually present as localized prostate cancer, stage I, stage II, even stage III prostate cancers and the majority of localized prostate cancers are actually fortunately quite curable with either surgery or radiation-based therapies.  

Unfortunately, not all are curable and some will recur despite these curative intent treatments and others might just be inherently more aggressive biologically and they could even present with metastatic disease or stage IV disease having spread to other sites outside of the prostate gland, even at diagnosis. 

When prostate cancer metastasizes or spreads, it commonly spreads by lymphatic vessels or by the bloodstream and most commonly, they tend to go to either lymph nodes or bones or some combination of both. More common areas of lymph node spread are in the pelvic areas, kind of near where the prostate gland is, or deep in the abdomen in an area called the retroperitoneum. And then bones more commonly could be in sort of the back or spine bones or in the pelvic bones, but it could go to other areas less common as well.  

Katherine:

What are common symptoms of advanced disease, and how are the symptoms managed? 

Dr. Gao:

So, with advanced disease, the symptoms can present in a variety of different ways.  

They’re often related to where the cancer has spread to. If there’s a tumor in the prostate gland itself or next to it, some patients might experience urinary symptoms, urinary frequency, feeling of incomplete emptying or a weak urinary flow. Or even pain or discomfort of leading with urination. That’s sort of the primary prostate tumor itself. Bone metastases can cause bone pain and commonly this involves bones in the spine or back or in the pelvis.   

There’s also a heightened risk of fractures with bone metastases and obviously that can sometimes cause pain. However, I think I should mention, many bone metastases actually don’t cause pain. It’s not uncommon that we see a bone scan or a CAT scan that the cancer is in multiple bones, but the patient actually, you know, I think fortunately, doesn’t feel any pain from that. 

Lymph node spread, I would say, rarely causes symptoms early on, but if there’s significant enlargement of these lymph nodes or in risking anatomic areas, sometimes the lymph nodes can cause discomfort or pain. Sometimes they can compress upon major veins or blood vessels or on the ureters that drain the kidneys and cause either blood clots or lower extremity swelling if it’s the major veins or cause kidney dysfunction because the ureters aren’t draining the kidneys appropriately. And then, I think in general, as with any advanced cancer, advanced prostate cancer can commonly cause fatigue and cause patients to just kind of generally feel unwell in sort of a hard to pinpoint type of way.  

I think it’s sort of the general toll that the cancer – the burden of the cancer is causing on the body and maybe taking, you know, essential nutrients or other things away from normal body organs or body cells.  

Katherine:

How are some of these symptoms managed?  

Dr. Gao:

So, pain, if people have pain, it’s typically managed with analgesics and pain medications, whether it’s Tylenol or ibuprofen. Other NSAID types of medications. Opiates and narcotic pain medications are commonly used for advanced prostate cancers as well to control and manage and treat the pain. And patients with cancers involving the bones that have become resistant to standard hormone therapy, we also commonly give medications called bisphosphonates. 

Zoledronic acid is a common one. Or a related medication called denosumab to try to reduce the risk of fractures, to strengthen the bones a bit. And these medications can also help with bone pain to some extent. And sometimes we treat other symptoms of cancer with medications that might help improve energy levels and improve the fatigue, for example.  

So, methylphenidate or methylphenidate  (Ritalin) is a common medication that is used to try to help with energy levels or reduced energy in advanced cancer patients. Sometimes steroid medications can do that as well, could be helpful. Appetite, reduced appetite with advanced cancer is not uncommon, although I think for prostate cancer, we see it to a lesser extent compared to other advanced cancers. 

There are other medications, steroids being one of them, and medications like mirtazapine or Remeron can be used to help try to simulate the appetite a little bit more. In terms of other symptoms, urinary symptoms, let’s say from the primary prostate tumor, that’s often co-managed with my colleagues in urology. There are medications that can be used to try to help with the urinary flow or stream in some situations or perhaps procedural interventions that might be able to help open up the urinary outlet a little bit more. Those things can be considered as well.  

Katherine:

I’d like to talk about what goes into deciding on a treatment pass. What testing is used to understand a patient’s individual disease? 

Dr. Gao:

There is a lot of testing that we do for – to try and characterize a patient’s individual disease and try to select an optimal management strategy for their specific cancer and their specific situation. 

We look at the biopsy, the pathology. The most common type of prostate cancer is called adenocarcinoma, but rarely we see certain other types under the microscope, things like neuroendocrine or small cell prostate cancers that tend to be treated in a different way. We look at things like the Gleason score.  

That tells us a bit more about sort of the aggressiveness of this cancer, as well as the PSA, you know, it’s a very good correlate for how the cancer is doing in general once somebody has been diagnosed with prostate cancer. For imaging tests, we commonly rely on imaging. We look at prostate MRIs to get an idea of the local extent of the prostate tumor. We get things like bone scans and CAT scans to look at the entire rest of the body to see if or where the cancer may have spread to.  

And there are newer imaging tests like the PSMA PET scan, which we commonly use now, which is a much more sensitive test for detecting prostate cancer in 2023 compared to traditional scans like CAT scans and bone scans. I also commonly make use of genetic testing and molecular information.  

So, for any patient with an advanced prostate cancer, I do recommend both what we call a germline test, which is testing for inherited cancer genes that a patient could have gotten from the parents and pass onto their kids, as well as somatic testing, which is testing the cancer itself to see what genetic mutations or alterations might’ve developed within their cancer. And that can actually factor into certain treatments that the patient may or may not be more likely to benefit from if they have these genetic mutations.  

Katherine:

Dr. Gao, a patient sent in this question prior to the program. What other genetic testing, beside BRCA markers, are important for deciding future targeted therapies and how are each of them used? 

Dr. Gao:

Yeah, that’s a great question. Targeted therapies have been used in a lot of different cancers and it’s only really within the past few years that we’re using them as a standard of care routinely in prostate cancers. So, BRCA II and BRCA I mutations are some of the more common mutations or genetic alterations that are targetable in prostate cancer. Recently, there have been multiple FDA approvals of different drugs that are called PARP inhibitor, which are able to target the cancer if they have BRCA II or BRCA I mutations.   

Beyond BRCA II and BRCA I, there’s a panel of what’s called homologous recombination repair genes and that’s defined differently in varying extents, depending on the specific drug. That has been FDA approved, but in general, it’s about 12-14 genes total and they actually include the BRCA II and BRCA I genes.  

So, some of the ones that have been…it seems like the data shows maybe more activity or better efficacy with these PARP inhibitors include a gene called PALB2, P-A-L-B 2. It’s not a very common mutation that we see, but it is something that we should look for because even if it’s not common overall for the patient who has it, it could be a very helpful and useful gene to know that that they have and it certainly would warrant treatment with a PARP inhibitor. 

The other sort of dozen  or so…10-12 genes in this homologous recombination repair pathway, the data, I would say, is still early and it is still somewhat limited in terms of how much people with those gene mutations truly benefit from these PARP inhibitors, but I do think it’s important to look for them, to know that if they do have one of these genetic mutations that it does make a PARP inhibitor an option for them. And then, beyond these HRR genes, I always look for something called a microsatellite instability or mismatched repair deficiency. These are sort of genetic features or really a panel of about four genes involved in a cellular process called – a DNA repair process called mismatch repair.  

For those patients that have either mismatched repair deficiency or microsatellite instability high cancers, I do recommend that they consider an immunotherapy medication called pembrolizumab which is FDA-approved regardless of cancer type for any MSI high or mismatched repair cancer and they’ve shown pretty solid activity for those kinds of cancers.  

Katherine:

Dr. Gao, now that we know what goes into understanding a patient’s disease, I’d like to talk about treatment, starting with treatment goals. How do goals vary by patient, if they vary at all? 

Dr. Gao:

Sure, yeah. I do think they vary and I think it is important to be clear about what the realistic goals of treatment might be so that the patient can make an informed decision on how the prostate cancer should be treated or managed. 

Some prostate cancers are highly curable, although there isn’t anything that’s 100 percent, right? And others are curable, but we acknowledge that there may still be a significant risk of relapse despite treatment. And maybe that rough percentage, the probability of cure and sort of the potential downsides or side effects of treatment, that’s something that the patient has to weigh in terms of whether they want to proceed with that treatment or not.  

And then, there are cancers, especially with advanced prostate cancers, that are unfortunately not curable, but yet treatments have the ability to significantly prolong somebody’s life, to slow the cancer progression down or even to shrink it, and to improve cancer-associated symptoms and other sources of distress that we talked about earlier. 

And so, with each patient, I think it is important to talk about these treatment goals because it may not be readily clear, is this a curable cancer or not? And it might not be clear how much benefit they might expect with treatment or are we talking about a marginal benefit? And then that way, you know, they can think about it, talk about it with their family, and kind of factor into their overall benefit risk calculation about whether to do something or not.  

Katherine:

Would you provide an overview of current treatment options for advanced disease? 

Dr. Gao:

Sure. So, it’s a big, very open-ended question, I think.  

So, I think you can divide it up into sort of the major treatment modalities, so things like radiation or radiation types of therapies, chemotherapy, hormonal therapies which are the mainstay of prostate cancer treatments, targeted therapies, and immunotherapies.   

Starting with hormonal therapies which are the backbone of prostate cancer treatments, for advanced prostate cancer, androgen deprivation therapy or ADT is often given indefinitely as the typical standard of care treatment and there are various forms of ADT, most commonly in the form of long-lasting injectable medications – leuprolide (Eligard/Lupron Depot), goserelin (Zoladex), sometimes degarelix (Firmagaon)  is used. And then more recently, there was an FDA approval a couple years ago of an oral pill called relugolix (Orgovyx), which is also a form of ADT or androgen deprivation therapy.   

These medications block the body’s ability to make testosterone which is important for prostate cancer survival and spread. In addition, abiraterone is an oral medication that is also considered a hormonal therapy. It blocks the production on androgens or male sex hormones outside of the testes. That includes the adrenal glands and some other tissues such as prostate cancer itself. And abiraterone (Zytiga) is commonly used in advanced prostate cancer management, in addition to androgen deprivation therapy whereas ADT blocks the testes from making testosterone and androgens, abiraterone blocks the production of androgens outside of the testes. 

And then finally, oral anti-androgen medications that block the prostate cancers from being able to detect androgens or male hormones and to block the androgen receptors on prostate cancers from sending cellular signals for growth and survival are also very commonly used.  

There are older anti-androgen medications like bicalutamide (Casodex), flutamide (Eulexin), lutamide, and there are newer ones, stronger versions, called enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). For most patients who present with advanced prostate cancer, I think this is much easier, ADT along with either abiraterone or one of the newer, stronger anti-androgens, is the standard of care for most advanced prostate cancer patients with metastatic disease.  

And then, sometimes for patients with higher volume or more aggressive cancers even in the group with metastatic disease, we even add on another treatment, usually chemotherapy, something called docetaxel for what we call triple therapy. And then, maybe that’s a segue to chemotherapy, so docetaxel chemotherapy is a common chemotherapy used for prostate cancer, certainly advanced prostate cancers. Cabazitaxel (Jevtana) is also a common chemotherapy in this situation. These two are related drugs in a family of drugs called taxane chemotherapies and basically they kind of block the trafficking of important components within cancer cells and cause the cancer cell death.  

Docetaxel (Taxotere) is the more commonly used one. It’s typically used earlier, before cabazitaxel. And like I said earlier, for certain patients with what we call high volume metastatic prostate cancer, it’s often used in combination with hormonal therapies early on, what we call upfront therapy for six cycles. If a patient doesn’t receive docetaxel up front, docetaxel is commonly used after progression, after the cancer has progressed on ADT and one of the oral hormone medications.  

Cabazitaxel is more commonly used after a patient has previously received or progressed on docetaxel. Both drugs have been evaluated in randomized Phase III clinical trials and have shown to provide efficacy for patients with advanced prostate cancers. 

In addition to these taxane chemotherapies, platinum chemotherapy, such as carboplatin or cisplatin, are sometimes used for advanced prostate cancers as well, especially for certain neuroendocrine or small cell prostate cancers. These are rarer cancers, but they tend to respond better to platinum-based chemotherapies.  

Or for certain what we call aggressive variant prostate cancers, these platinum-based chemotherapies are also used in combination with either one of the taxanes or with another chemotherapy drug called etoposide. In terms of other treatment modalities, I think recently what we call radiotherapeutics or radioligand therapies have gotten a lot of press with the approval of a new medication called lutetium PSMA or 177 lutetium PSMA 617 (Pluvicto). 

The brand name for that in the U.S. is Pluvicto and what this is is a drug that’s a small molecule that binds to PSMA, which is a protein highly expressed in close to 90% of prostate cancer, advanced prostate cancers. And the small molecule will home to the cancer and it’s linked to radioactive lutetium and the lutetium will decay in that area and lead to cancer cell death.  

So, Pluvicto or lutetium was FDA approved in spring of 2022 based on randomized Phase III trials that show significant efficacy for patients with metastatic castration-resistant prostate cancer who have previously received a second-generation androgen receptor pathway inhibitor, such as abiraterone and enzalutamide, as well as a taxane chemotherapy, like docetaxel or cabazitaxel.  

The medication is given intravenously, once every six weeks, for up to six doses, and there are ongoing clinical trials, actually, that are trying to evaluate this medication in earlier settings where patients haven’t gotten prior chemotherapy before. There was a press release from about half a year ago stating that they’re seeing some early encouraging signs of efficacy with this drug, even in patients who had never received chemotherapy before, so it may be a medication that is going to be used more and more so in more patients even earlier in their course of disease. 

Katherine:

This actually leads me to my next question which is about research news. 

Prostate cancer research is evolving quickly, like so many other cancers. And it’s important for patients to stay up to date on developing news. So, are there research advances that patients should be aware of? 

Dr. Gao:

Yeah, I mean some of the treatments that I just mentioned, PARP inhibitors, pembrolizumab (Keytruda) for MSI higher and mismatch repair deficient tumors and lutetium. Those have come out of recent major clinical trials and have become the standard of care in a lot of different…in various different settings for patients. And there are always new research trials, clinical trials, that are going to either move some of these established treatments to earlier lines of setting, earlier lines of treatment, or using them in maybe combination with other drugs where we might learn that they’re more useful if we combine it with another drug or maybe combine it with hormone treatments earlier rather than later. 

So, there are always clinical trials for advanced prostate cancer. There are even newer trials, novel therapies, completely new treatments that have been studied in the laboratory in say petri dish models of cancer or animal, mouse models of prostate cancer, but have shown enough early exciting data to try to move them into human beings and hopefully help advanced prostate cancer patients. 

Katherine:

Dr. Gao, if a patient is feeling like they’re not getting proper care or if they’re just not comfortable with their care team, what steps would you recommend they take to change the situation? 

Dr. Gao:

Yeah, I think that’s a difficult question to answer and it depends on sort of what the specifics are, but I will always encourage people to be up front with their providers, with their oncologists and their oncology team. I think it’s… it really is a collaboration and it really needs mutual trust and open communication.  

And to be able to say these are the things that I wish could be a bit better or not that different or could you clarify this or answer this or what about this idea or this thing that maybe I heard about. See what their thoughts are. I think clear communication is always important and it shouldn’t – I tell my patients that I view my role as sort of advising them about what the reasonable treatment or management strategies might be in their situation and what the data shows and what is recommended. 

But ultimately, it is a shared decision and the patient is in charge of their own body and own health and they can make the decision on what makes sense for them. So, again, I think it’ s a two-way street and open communication is the most important thing.  

Katherine:

As we wrap up, Dr. Gao, I’d like to get your thoughts. How do you feel about where we stand with advanced prostate cancer care? 

Dr. Gao:

Yeah. I think there have been a lot of advances in advanced prostate cancer care in recent years. Newer and better treatment strategies seem to come along every couple of years and I think what we’ve seen for advanced prostate cancer patients over the past, really, since probably 2015 or so, is a significant improvement in outcomes, long-term outcomes like survival and slowing down of the cancer. 

And it’s… I think it’s important to acknowledge that and to acknowledge that the clinical trials in recent years have really led to a lot of improvements and really the hope that in the coming years, there’s going to be additional research, additional clinical trials, newer treatments hopefully, that will continue to improve outcomes for advanced prostate cancer patients. I also think that it’s really critical to evaluate the specific patients’ cancer characteristics, things like the genetic testing that I mentioned earlier, as well as their sort of life situations and other medical comorbidities to come to a shared decision about what makes the most sense in terms of their cancer management.  

Genetic testing might open up the option for certain FDA-approved therapies or consideration of certain targeted therapies that still might be in clinical trials. And clinical trials, again, are also an option for additional treatment strategies that otherwise would not be available. 

Katherine:

Dr. Gao, thank you so much for taking the time to join us today. 

Dr. Gao:

You’re welcome. Thanks for having me. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this program. It will help us as we plan future webinars. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us. 

Advanced Prostate Cancer: How to Access the Best Care and Treatment for YOU

Advanced Prostate Cancer: How to Access the Best Care and Treatment for YOU from Patient Empowerment Network on Vimeo.

Progress in advanced prostate cancer has led to more personalized treatment options and individualized care for people with this diagnosis. Dr. Xin Gao discusses how the results of essential testing can help guide a patient’s prognosis and treatment path, reviews available therapies, and shares advice for self-advocacy.

Bio:
Dr. Xin Gao is a Medical Oncologist at Massachusetts General Hospital. Learn more about Dr. Gao.

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Transcript:

Katherine:

Hello and welcome. I’m your host Katherine Banwell. Today’s program focuses on how people with advanced prostate cancer can access the best treatment in care. We’ll review essential testing, discuss the latest research, and share tips for self-advocacy. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to a resource guide. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars.  

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Xin Gao. Dr. Gao, welcome. Would you please introduce yourself? 

Dr. Gao:

Yeah. Thank you very much for having me. My name is Xin Gao. I’m a medical oncologist at Mass General Cancer Center in Boston, Massachusetts. I focus on prostate cancer and other cancers involving the urinary system. I’m also involved in our clinical trials program where we’re studying newer and what we hope are better treatments for these types of cancers.  

Katherine:

Well, thank you so much for joining us today. I know you’re a busy guy.  

Dr. Gao:

I’m happy to be here.  

Katherine:

Good. Dr. Gao, this program is focusing on advanced prostate cancer. Would you walk us through how the disease progresses in each stage? 

Dr. Gao:

Sure. I think advanced prostate cancer can mean a lot of different things, but in general, it means a prostate cancer that has either spread out from the prostate gland itself to other areas of the body or has recurred despite either surgery or radiation-based therapy to the primary prostate tumor. 

In each of these situations, typically the focus would on medication types of treatments and we think about advanced prostate cancer as either hormone-sensitive or hormone-resistant, or the other term in the field for it would be castration-resistant, meaning that the prostate cancer is either sensitive to hormonal therapies or perhaps it’s no longer sensitive to the most common type of hormone therapy called androgen deprivation therapy. So, those are sort of the ways that the cancer can progress, and typically all these cancers start as hormone-sensitive prostate cancers and over time, they may evolve and become resistant and become what we call castration-resistant prostate cancer. 

Katherine:

Okay. So, they’re not numbered as in a lot of other cancers, like stage I, stage II?  

Dr. Gao:

Meaning by stage, oh. So, there are stages. All advanced prostate cancers are by definition stage IV. All advanced cancers, in general, are stage IV but advanced prostate cancer would be stage IV. Most prostate cancers actually present as localized prostate cancer, stage I, stage II, even stage III prostate cancers and the majority of localized prostate cancers are actually fortunately quite curable with either surgery or radiation-based therapies.  

Unfortunately, not all are curable and some will recur despite these curative intent treatments and others might just be inherently more aggressive biologically and they could even present with metastatic disease or stage IV disease having spread to other sites outside of the prostate gland, even at diagnosis. 

When prostate cancer metastasizes or spreads, it commonly spreads by lymphatic vessels or by the bloodstream and most commonly, they tend to go to either lymph nodes or bones or some combination of both. More common areas of lymph node spread are in the pelvic areas, kind of near where the prostate gland is, or deep in the abdomen in an area called the retroperitoneum. And then bones more commonly could be in sort of the back or spine bones or in the pelvic bones, but it could go to other areas less common as well.  

Katherine:

What are common symptoms of advanced disease, and how are the symptoms managed? 

Dr. Gao:

So, with advanced disease, the symptoms can present in a variety of different ways.  

They’re often related to where the cancer has spread to. If there’s a tumor in the prostate gland itself or next to it, some patients might experience urinary symptoms, urinary frequency, feeling of incomplete emptying or a weak urinary flow. Or even pain or discomfort of leading with urination. That’s sort of the primary prostate tumor itself. Bone metastases can cause bone pain and commonly this involves bones in the spine or back or in the pelvis.   

There’s also a heightened risk of fractures with bone metastases and obviously that can sometimes cause pain. However, I think I should mention, many bone metastases actually don’t cause pain. It’s not uncommon that we see a bone scan or a CAT scan that the cancer is in multiple bones, but the patient actually, you know, I think fortunately, doesn’t feel any pain from that. 

Lymph node spread, I would say, rarely causes symptoms early on, but if there’s significant enlargement of these lymph nodes or in risking anatomic areas, sometimes the lymph nodes can cause discomfort or pain. Sometimes they can compress upon major veins or blood vessels or on the ureters that drain the kidneys and cause either blood clots or lower extremity swelling if it’s the major veins or cause kidney dysfunction because the ureters aren’t draining the kidneys appropriately. And then, I think in general, as with any advanced cancer, advanced prostate cancer can commonly cause fatigue and cause patients to just kind of generally feel unwell in sort of a hard to pinpoint type of way.  

I think it’s sort of the general toll that the cancer – the burden of the cancer is causing on the body and maybe taking, you know, essential nutrients or other things away from normal body organs or body cells.  

Katherine:

How are some of these symptoms managed?  

Dr. Gao:

So, pain, if people have pain, it’s typically managed with analgesics and pain medications, whether it’s Tylenol or ibuprofen. Other NSAID types of medications. Opiates and narcotic pain medications are commonly used for advanced prostate cancers as well to control and manage and treat the pain. And patients with cancers involving the bones that have become resistant to standard hormone therapy, we also commonly give medications called bisphosphonates. 

Zoledronic acid is a common one. Or a related medication called denosumab to try to reduce the risk of fractures, to strengthen the bones a bit. And these medications can also help with bone pain to some extent. And sometimes we treat other symptoms of cancer with medications that might help improve energy levels and improve the fatigue, for example.  

So, methylphenidate or methylphenidate  (Ritalin) is a common medication that is used to try to help with energy levels or reduced energy in advanced cancer patients. Sometimes steroid medications can do that as well, could be helpful. Appetite, reduced appetite with advanced cancer is not uncommon, although I think for prostate cancer, we see it to a lesser extent compared to other advanced cancers. 

There are other medications, steroids being one of them, and medications like mirtazapine or Remeron can be used to help try to simulate the appetite a little bit more. In terms of other symptoms, urinary symptoms, let’s say from the primary prostate tumor, that’s often co-managed with my colleagues in urology. There are medications that can be used to try to help with the urinary flow or stream in some situations or perhaps procedural interventions that might be able to help open up the urinary outlet a little bit more. Those things can be considered as well.  

Katherine:

I’d like to talk about what goes into deciding on a treatment pass. What testing is used to understand a patient’s individual disease? 

Dr. Gao:

There is a lot of testing that we do for – to try and characterize a patient’s individual disease and try to select an optimal management strategy for their specific cancer and their specific situation. 

We look at the biopsy, the pathology. The most common type of prostate cancer is called adenocarcinoma, but rarely we see certain other types under the microscope, things like neuroendocrine or small cell prostate cancers that tend to be treated in a different way. We look at things like the Gleason score.  

That tells us a bit more about sort of the aggressiveness of this cancer, as well as the PSA, you know, it’s a very good correlate for how the cancer is doing in general once somebody has been diagnosed with prostate cancer. For imaging tests, we commonly rely on imaging. We look at prostate MRIs to get an idea of the local extent of the prostate tumor. We get things like bone scans and CAT scans to look at the entire rest of the body to see if or where the cancer may have spread to.  

And there are newer imaging tests like the PSMA PET scan, which we commonly use now, which is a much more sensitive test for detecting prostate cancer in 2023 compared to traditional scans like CAT scans and bone scans. I also commonly make use of genetic testing and molecular information.  

So, for any patient with an advanced prostate cancer, I do recommend both what we call a germline test, which is testing for inherited cancer genes that a patient could have gotten from the parents and pass onto their kids, as well as somatic testing, which is testing the cancer itself to see what genetic mutations or alterations might’ve developed within their cancer. And that can actually factor into certain treatments that the patient may or may not be more likely to benefit from if they have these genetic mutations.  

Katherine:

Dr. Gao, a patient sent in this question prior to the program. What other genetic testing, beside BRCA markers, are important for deciding future targeted therapies and how are each of them used? 

Dr. Gao:

Yeah, that’s a great question. Targeted therapies have been used in a lot of different cancers and it’s only really within the past few years that we’re using them as a standard of care routinely in prostate cancers. So, BRCA II and BRCA I mutations are some of the more common mutations or genetic alterations that are targetable in prostate cancer. Recently, there have been multiple FDA approvals of different drugs that are called PARP inhibitor, which are able to target the cancer if they have BRCA II or BRCA I mutations.   

Beyond BRCA2 and BRCA1, there’s a panel of what’s called homologous recombination repair genes and that’s defined differently in varying extents, depending on the specific drug. That has been FDA approved, but in general, it’s about 12-14 genes total and they actually include the BRCA2 and BRCA1 genes.  

So, some of the ones that have been…it seems like the data shows maybe more activity or better efficacy with these PARP inhibitors include a gene called PALB2, P-A-L-B 2. It’s not a very common mutation that we see, but it is something that we should look for because even if it’s not common overall for the patient who has it, it could be a very helpful and useful gene to know that that they have and it certainly would warrant treatment with a PARP inhibitor. 

The other sort of dozen  or so…10-12 genes in this homologous recombination repair pathway, the data, I would say, is still early and it is still somewhat limited in terms of how much people with those gene mutations truly benefit from these PARP inhibitors, but I do think it’s important to look for them, to know that if they do have one of these genetic mutations that it does make a PARP inhibitor an option for them. And then, beyond these HRR genes, I always look for something called a microsatellite instability or mismatched repair deficiency. These are sort of genetic features or really a panel of about four genes involved in a cellular process called – a DNA repair process called mismatch repair.  

For those patients that have either mismatched repair deficiency or microsatellite instability high cancers, I do recommend that they consider an immunotherapy medication called pembrolizumab which is FDA-approved regardless of cancer type for any MSI high or mismatched repair cancer and they’ve shown pretty solid activity for those kinds of cancers.  

Katherine:

Dr. Gao, now that we know what goes into understanding a patient’s disease, I’d like to talk about treatment, starting with treatment goals. How do goals vary by patient, if they vary at all? 

Dr. Gao:

Sure, yeah. I do think they vary and I think it is important to be clear about what the realistic goals of treatment might be so that the patient can make an informed decision on how the prostate cancer should be treated or managed. 

Some prostate cancers are highly curable, although there isn’t anything that’s 100 percent, right? And others are curable, but we acknowledge that there may still be a significant risk of relapse despite treatment. And maybe that rough percentage, the probability of cure and sort of the potential downsides or side effects of treatment, that’s something that the patient has to weigh in terms of whether they want to proceed with that treatment or not.  

And then, there are cancers, especially with advanced prostate cancers, that are unfortunately not curable, but yet treatments have the ability to significantly prolong somebody’s life, to slow the cancer progression down or even to shrink it, and to improve cancer-associated symptoms and other sources of distress that we talked about earlier. 

And so, with each patient, I think it is important to talk about these treatment goals because it may not be readily clear, is this a curable cancer or not? And it might not be clear how much benefit they might expect with treatment or are we talking about a marginal benefit? And then that way, you know, they can think about it, talk about it with their family, and kind of factor into their overall benefit risk calculation about whether to do something or not.  

Katherine:

Would you provide an overview of current treatment options for advanced disease? 

Dr. Gao:

Sure. So, it’s a big, very open-ended question, I think.  

So, I think you can divide it up into sort of the major treatment modalities, so things like radiation or radiation types of therapies, chemotherapy, hormonal therapies which are the mainstay of prostate cancer treatments, targeted therapies, and immunotherapies.   

Starting with hormonal therapies which are the backbone of prostate cancer treatments, for advanced prostate cancer, androgen deprivation therapy or ADT is often given indefinitely as the typical standard of care treatment and there are various forms of ADT, most commonly in the form of long-lasting injectable medications – leuprolide (Eligard/Lupron Depot), goserelin (Zoladex), sometimes degarelix (Firmagaon)  is used. And then more recently, there was an FDA approval a couple years ago of an oral pill called relugolix (Orgovyx), which is also a form of ADT or androgen deprivation therapy.   

These medications block the body’s ability to make testosterone which is important for prostate cancer survival and spread. In addition, abiraterone is an oral medication that is also considered a hormonal therapy. It blocks the production on androgens or male sex hormones outside of the testes. That includes the adrenal glands and some other tissues such as prostate cancer itself. And abiraterone (Zytiga) is commonly used in advanced prostate cancer management, in addition to androgen deprivation therapy whereas ADT blocks the testes from making testosterone and androgens, abiraterone blocks the production of androgens outside of the testes. 

And then finally, oral anti-androgen medications that block the prostate cancers from being able to detect androgens or male hormones and to block the androgen receptors on prostate cancers from sending cellular signals for growth and survival are also very commonly used.  

There are older anti-androgen medications like bicalutamide (Casodex), flutamide (Eulexin), lutamide, and there are newer ones, stronger versions, called enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). For most patients who present with advanced prostate cancer, I think this is much easier, ADT along with either abiraterone or one of the newer, stronger anti-androgens, is the standard of care for most advanced prostate cancer patients with metastatic disease.  

And then, sometimes for patients with higher volume or more aggressive cancers even in the group with metastatic disease, we even add on another treatment, usually chemotherapy, something called docetaxel for what we call triple therapy. And then, maybe that’s a segue to chemotherapy, so docetaxel chemotherapy is a common chemotherapy used for prostate cancer, certainly advanced prostate cancers. Cabazitaxel (Jevtana) is also a common chemotherapy in this situation. These two are related drugs in a family of drugs called taxane chemotherapies and basically they kind of block the trafficking of important components within cancer cells and cause the cancer cell death.  

Docetaxel (Taxotere) is the more commonly used one. It’s typically used earlier, before cabazitaxel. And like I said earlier, for certain patients with what we call high volume metastatic prostate cancer, it’s often used in combination with hormonal therapies early on, what we call upfront therapy for six cycles. If a patient doesn’t receive docetaxel up front, docetaxel is commonly used after progression, after the cancer has progressed on ADT and one of the oral hormone medications.  

Cabazitaxel is more commonly used after a patient has previously received or progressed on docetaxel. Both drugs have been evaluated in randomized Phase III clinical trials and have shown to provide efficacy for patients with advanced prostate cancers. 

In addition to these taxane chemotherapies, platinum chemotherapy, such as carboplatin or cisplatin, are sometimes used for advanced prostate cancers as well, especially for certain neuroendocrine or small cell prostate cancers. These are rarer cancers, but they tend to respond better to platinum-based chemotherapies.  

Or for certain what we call aggressive variant prostate cancers, these platinum-based chemotherapies are also used in combination with either one of the taxanes or with another chemotherapy drug called etoposide. In terms of other treatment modalities, I think recently what we call radiotherapeutics or radioligand therapies have gotten a lot of press with the approval of a new medication called lutetium PSMA or 177 lutetium PSMA 617 (Pluvicto). 

The brand name for that in the U.S. is Pluvicto and what this is is a drug that’s a small molecule that binds to PSMA, which is a protein highly expressed in close to 90 percent of prostate cancer, advanced prostate cancers. And the small molecule will home to the cancer and it’s linked to radioactive lutetium and the lutetium will decay in that area and lead to cancer cell death.  

So, Pluvicto or lutetium was FDA approved in spring of 2022 based on randomized Phase III trials that show significant efficacy for patients with metastatic castration-resistant prostate cancer who have previously received a second-generation androgen receptor pathway inhibitor, such as abiraterone and enzalutamide, as well as a taxane chemotherapy, like docetaxel or cabazitaxel.  

The medication is given intravenously, once every six weeks, for up to six doses, and there are ongoing clinical trials, actually, that are trying to evaluate this medication in earlier settings where patients haven’t gotten prior chemotherapy before. There was a press release from about half a year ago stating that they’re seeing some early encouraging signs of efficacy with this drug, even in patients who had never received chemotherapy before, so it may be a medication that is going to be used more and more so in more patients even earlier in their course of disease. 

Katherine:

This actually leads me to my next question which is about research news. 

Prostate cancer research is evolving quickly, like so many other cancers. And it’s important for patients to stay up to date on developing news. So, are there research advances that patients should be aware of? 

Dr. Gao:

Yeah, I mean some of the treatments that I just mentioned, PARP inhibitors, pembrolizumab (Keytruda) for MSI higher and mismatch repair deficient tumors and lutetium. Those have come out of recent major clinical trials and have become the standard of care in a lot of different…in various different settings for patients. And there are always new research trials, clinical trials, that are going to either move some of these established treatments to earlier lines of setting, earlier lines of treatment, or using them in maybe combination with other drugs where we might learn that they’re more useful if we combine it with another drug or maybe combine it with hormone treatments earlier rather than later. 

So, there are always clinical trials for advanced prostate cancer. There are even newer trials, novel therapies, completely new treatments that have been studied in the laboratory in say petri dish models of cancer or animal, mouse models of prostate cancer, but have shown enough early exciting data to try to move them into human beings and hopefully help advanced prostate cancer patients. 

Katherine:

Dr. Gao, if a patient is feeling like they’re not getting proper care or if they’re just not comfortable with their care team, what steps would you recommend they take to change the situation? 

Dr. Gao:

Yeah, I think that’s a difficult question to answer and it depends on sort of what the specifics are, but I will always encourage people to be up front with their providers, with their oncologists and their oncology team. I think it’s… it really is a collaboration and it really needs mutual trust and open communication.  

And to be able to say these are the things that I wish could be a bit better or not that different or could you clarify this or answer this or what about this idea or this thing that maybe I heard about. See what their thoughts are. I think clear communication is always important and it shouldn’t – I tell my patients that I view my role as sort of advising them about what the reasonable treatment or management strategies might be in their situation and what the data shows and what is recommended. 

But ultimately, it is a shared decision and the patient is in charge of their own body and own health and they can make the decision on what makes sense for them. So, again, I think it’ s a two-way street and open communication is the most important thing.  

Katherine:

As we wrap up, Dr. Gao, I’d like to get your thoughts. How do you feel about where we stand with advanced prostate cancer care? 

Dr. Gao:

Yeah. I think there have been a lot of advances in advanced prostate cancer care in recent years. Newer and better treatment strategies seem to come along every couple of years and I think what we’ve seen for advanced prostate cancer patients over the past, really, since probably 2015 or so, is a significant improvement in outcomes, long-term outcomes like survival and slowing down of the cancer. 

And it’s… I think it’s important to acknowledge that and to acknowledge that the clinical trials in recent years have really led to a lot of improvements and really the hope that in the coming years, there’s going to be additional research, additional clinical trials, newer treatments hopefully, that will continue to improve outcomes for advanced prostate cancer patients. I also think that it’s really critical to evaluate the specific patients’ cancer characteristics, things like the genetic testing that I mentioned earlier, as well as their sort of life situations and other medical comorbidities to come to a shared decision about what makes the most sense in terms of their cancer management.  

Genetic testing might open up the option for certain FDA-approved therapies or consideration of certain targeted therapies that still might be in clinical trials. And clinical trials, again, are also an option for additional treatment strategies that otherwise would not be available. 

Katherine:

Dr. Gao, thank you so much for taking the time to join us today. 

Dr. Gao:

You’re welcome. Thanks for having me. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this program. It will help us as we plan future webinars. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us. 

PODCAST: What Do You Need to Know About Emerging Endometrial Cancer Research?

 

Endometrial cancer treatment and research is evolving quickly. Dr. Emily Ko provides an update on new and emerging approaches, explains how these therapies work to treat endometrial cancer, and shares tips for partnering with your team on key decisions.
 
Dr. Emily Ko is a gynecologic oncologist and Associate Professor of Obstetrics and Gynecology at the University of Pennsylvania. Learn more about Dr. Ko.

See More from Evolve Endometrial Cancer

Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. Today’s program focuses on helping patients with endometrial cancer learn more about evolving research and treatments. We’re also going to discuss how patients can collaborate with their team on care decisions. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar. 

At the end of the program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Emily Ko. Dr. Ko, welcome. Would you please introduce yourself? 

Dr. Ko:

Surely. Thank you so much. My name is Dr. Emily Ko, and I am a gynecologic oncologist. Currently, I’m an associate professor at the University of Pennsylvania, and as part of my daily work, I see patients, I provide surgical and medical treatments for gynecologic cancers, and I also am a researcher involved particularly in endometrial cancer. 

Katherine:

Thank you so much for taking the time out of your schedule to join us today. 

Dr. Ko:

Thank you. 

Katherine:

Well, let’s start by learning about the latest research news. Just this June, endometrial cancer researchers from around the world met to discuss their findings at the annual American Society of Clinical Oncology meeting, or ASCO, in Chicago. Can you walk us through the highlights that patients should know about? 

Dr. Ko:

Sure. So, the ASCO meeting is a very big meeting that happens once a year in June, and really, it is a national – actually, international – meeting where the biggest breakthroughs in cancer therapy are really presented and discussed. 

So, within the field of gynecologic cancer and specifically endometrial cancer, we really saw a couple breakthrough clinical trial results, if you will. The two specific trials that have hit the spotlight – and, it was presented at ASCO; they were also previously presented at the Society of Gynecologic Oncology annual meeting in March of 2023. These two trials – one of them is called GY018, and the other one is called RUBY, and these two trials specifically were geared at patients with endometrial cancer of either advanced stage, meaning stage III or IV at diagnosis, or patients who have recurrent endometrial cancer.  

And, these both trials were very large, multisite, international trials enrolling a huge number of patients. They were randomized controlled trials, meaning that they were specifically testing what we call a standard therapy, Taxol-carboplatin, versus a standard therapy plus a newer agent, and that newer agent falls in the realm of an immunotherapy drug. 

So, with this kind of novel approach, where we’re combining standardly used chemotherapy plus a newer immunotherapy drug, the question was if you did this combination, would patients have a better outcome? And, in fact, the groundbreaking news was that yes, patients did have a better outcome with this new combination of therapy, and this was shown in various forms of results. 

One of the primary outcomes is always something called survival, and with the GY018, they looked at progression-free survival as a primary outcome, and it did show that patients on this new combination did better with progression-free survival. And the difference was about median of about three months. Now, that may not sound like a whole lot. However, in the realm of cancer therapy, when you take a very large group of patients, that was a meaningful difference that was statistically significant. 

And furthermore, as we’re moving forward with our therapy drugs, we are moving into this era of targeted therapy, precision medicine, where we’re really trying to hone into more the specifics of the biology of each person’s cancer, and not treating everyone the same. 

What’s interesting with these two trials is when they looked at different subpopulations of patients with advanced or recurrent endometrial cancer, whether they had a type of endometrial cancer that was considered MSI-high, or a microsatellite instable type of cancer, which basically refers to a certain biology of these endometrial cancers, it has to deal with how the cells – the cancer cells – behave, how they’re able to not follow the rules and be able to replicate themselves. 

The patients who are MSI-high particularly had a really great response with this chemotherapy, so it was even beyond just a three-month difference. With that being said, even in patients who are what we call microsatellite-stable, who didn’t have this unique signature, they still saw a benefit with this novel combination, and to add to that, the nice thing about it is the toxicities were not bad. Even this new combination was very well-tolerated. 

It was not a high rate of severe toxicities or side effects, if you will, and that actually, the great majority of patients were able to stay on this therapy and really get through – complete the therapy course. 

So, there are some sort of nuanced differences between the two trials I mentioned, GY018 versus the RUBY. And some of those details are with regards to the even specific subtype of endometrial cancer, which we haven’t talked about yet, for example, uterine carcinosarcoma versus uterine serous carcinoma, uterine clear cell, uterine endometrioid – these are all specific subtypes of endometrial cancer. So there are some nuances where the RUBY trial was able to include patients with uterine carcinosarcoma, whereas the GY018 did not. 

But suffice it to say, now we have enough data that virtually all endometrial cancer patients with advanced stage, regardless of what histology, there is essentially a trial that can apply to you where it demonstrated this added benefit to doing this novel combination, and that was found with microsatellite-stable patients as well as microsatellite-instable in both randomized controlled trials that I mentioned. 

Katherine:

Such exciting news! That’s great! Well, beyond ASCO, Dr. Ko, are there other research or treatment advances that patients should know about?  

Dr. Ko:

Certainly. Like I mentioned, we’re really moving towards the realm of treating with a targeted therapy approach, and within endometrial cancer, the prior paradigm was much simpler, but really not in the space of target therapy. So, for example, what does that mean? 

So, as we’re realizing that there are very unique biologic signatures to different patients’ endometrial cancer – there could be, for example, some cancers that are particularly receptive to hormonal therapy, meaning their specific cancer, when we send it for detailed – we call it genomic or somatic testing, we can discover, oh, they have estrogen-receptor-positive, progesterone-receptor-positive, and so, those type of cancers may be very responsive to hormonal-based therapy, and in that space, we have a standard available drugs, but we also have clinical trials that are trying newer drugs. 

If, for example, the standard aromatase inhibitor or the standard progesterone agent may be helpful, but there are even more in that space that this point – CDK inhibitors that you can combine with these aromatase inhibitors or hormonal agents that have been around for longer that have shown a lot of promise, a lot of data in breast cancer. But now we’re realizing, wow, there could be some efficacy in endometrial cancer as well, so that’s just one example. 

And there’s other unique biologic gene signatures, again, kind of a good list now out there, that are being studied in various clinical trials, whether they’re PARP inhibitors, whether they’re drugs that target CCNE1, whether they’re drugs that target ARID1A, so there are actually many more that are available. So, they’re really expanding the opportunity for treatment for endometrial cancer patients. 

Katherine:

Well, you just mentioned clinical trials, and I think it’s a good topic to cover a little bit. Why is it important for patients to actually consider enrolling? What are the benefits for them? 

Dr. Ko:

Sure.

So, while we certainly have a good armamentarium of standard-of-care therapies already, and I should mention that does include our classic chemotherapy drugs like paclitaxel (Abraxane), carboplatin (Paraplatin), and even doxorubicin (Adriamycin), if you will, or doxorubicin Hcl (Doxil), there are the immunotherapy drugs now that have become standard of care as well, like pembrolizumab (Keytruda), but sometimes, despite using those best available drugs, the cancer unfortunately either continues to grow or you had a good response, but somehow it shows up again – the cancer shows up again – and so, then, we’re looking for additional opportunities, additional therapies. 

And so, some of the best opportunities are actually to consider these clinical trials. The way that clinical trials are designed is that they always are going  to provide you at least a backbone of a standard available therapy, so you’re never going to get less than what would be considered standard of care. 

But, what they’re doing is they’re usually partnering another drug – a more novel therapy – or they’re basically testing a more novel therapy that could be more targeted, that could potentially have better efficacy than what’s already available standardly. And so, the value of that is that you could have an opportunity to have a therapy that could work even better.  

When you’ve tried something already, unfortunately, the cancer has grown, there is still opportunity, and while you’re on a clinical trial, I think one of the huge benefits is it’s very regulated. You are monitored so closely because at the base of all of this is safety. There is never going to be a drug or therapy that’s going to be administered to a patient without ensuring that there’s absolute safety for that patient, and so, that’s a way that you really have opportunity to get more treatment that could really help your cancer condition and do it in a very, very safe, formal fashion. 

Katherine:

And ultimately help others as well, in the future.  

Dr. Ko:

Exactly, absolutely, because as you’re participating in this process – and, of course, it’s a voluntary process to participate on a clinical trial, so we so appreciate all the patients who, in the past, have participated and are willing to participate in the future, but allows us also to really gather a lot of information to really inform cancer treatment for all the patients coming down the road, and those could be anyone. They could be our neighbors, our friends, our own family members, and that could really be so helpful to everyone that’s going through this type of thing. 

Katherine:

Absolutely, yeah. I’d like to back up a bit and talk about what endometrial cancer is. It’s often referred to as uterine cancer. So, are they the same thing? Are these terms interchangeable? 

Dr. Ko:

Sure, it’s a great question. So, endometrial cancer refers to cancer that starts in what I call the lining of the uterine cavity. So, inside the uterus, there’s a uterine cavity, and there’s a tissue that coats that cavity, and that’s called the endometrium. So, endometrial cancer is basically when cancer cells start growing from that tissue. And, of course, since that exists in the uterus, of course, it’s considered uterine cancer, and we’re just being a little bit more specific when we say endometrial cancer. But, of course, endometrial cancer is the most common form of uterine cancer by far, so in some ways, it’s almost – it’s synonymous.  

Katherine:

How is endometrial cancer staged? 

Dr. Ko:

So, the most classic, rigorous way to stage endometrial cancer is through a surgical procedure. So, what that usually involves is it does include a hysterectomy, removing the uterus and the cervix, usually also includes removing the fallopian tubes and the ovaries. 

And, at the same time, the surgeon will do a very thorough assessment of the abdominal pelvic cavity, basically looking around all those areas to see if there’s any signs of visible disease, anything they can see that looks like it could be tumor deposits in the abdominal cavity. If anything is seen, those deposits will be removed and biopsied, so that’s part of the staging procedure. 

And additionally, it’s important to try to assess the lymph nodes, typically. So, there are lymph nodes in the pelvic area, and then, higher up along the aortic area, and so, there are different surgical techniques that we can use to basically test or sample some of those lymph nodes, be able to remove them, send them to the pathologist, look under the microscope to see if there are any microscopic cancer cells that have traveled to those lymph nodes. 

So, that is all part of a surgical procedure, and with all the information collected from those tissue samples that are removed from the body and sent to the pathologist, but the pathologist then reviews all of that under a microscope, and then can issue a very thorough report describing where the cancer cells are located, and by definition, where the cancer cells are located then defines what the stage is of the cancer. 

Katherine:

Can you give me an example? 

Dr. Ko:

Of course. So, for example, if the cancer cells are located only in the uterus, and they’re not found anywhere else, then that is a stage I. If the cancer cells have traveled to the cervix area specifically, this we call a cervical stroma, that becomes a stage II. If the cancer cells have, for example, traveled to the fallopian tubes, or the ovaries, or the lymph nodes, then that becomes a stage III, and there are sort of substages within those categories as well. 

Katherine:

But stage III would be the highest or most severe? 

Dr. Ko:

So, there’s stage III, and then there’s actually stage IV. So, if the cancer cells have traveled outside of the pelvis into the abdominal area, then we consider that a stage IV. 

Katherine:

And that would be considered advanced endometrial cancer? 

Dr. Ko:

Right. So, by definition, “advanced” typically refers to stage III or IV. 

Katherine:

I see, okay. Now that we understand more about the disease itself, I’d like to talk about the treatments that are currently available. You mentioned chemotherapy, but what else is available for people? 

Dr. Ko:

Absolutely. So, treatment for endometrial cancer is usually some combination of surgery, and then it may be followed by possibly chemotherapy, as well as radiation, and sometimes, it may be a combination of all three treatments, or sometimes, it’s a combination of one or two of those, depending on the exact stage, depending on the exact cell type, and some of the other factors. 

Katherine:

Are hormonal therapies used as well, and targeted therapies? 

Dr. Ko:

Yes. 

Katherine:

I know they are in other cancers. 

Dr. Ko:

Yes. And so, I think the question is where do those come into play? So, I would say the usual algorithm most commonly would be that surgery is done first, as the most common first step, and then, based on the information obtained from surgery and the pathology report that comes from that, then there’s usually some type of a recommendation about should there be a second stepped treatment, and that frequently can be chemotherapy/radiation.  

Now, the areas where targeted therapy – for example, immunotherapy – where does that come in? So, that now has come into the – I would call it the second stage. We’re combining it with the classic chemotherapy drugs – Taxol-carboplatin, for example. That’s one example where it could come into play. Another example could come into play where a patient had gone through classic Taxol/paclitaxel and carboplatin, then had cancer come back, and so, that could be another instance where that pembrolizumab or pembro with lenvatinib (Lenvima) combination can be used in the setting of recurrence. 

Now, we could also say, hey, if your cancer type has those hormonal receptors present or is some type of what we call endometrioid histology, and we think that hormonal therapy may be more effective in that case, then that could also be used in a setting where the cancer has kind of grown again, the cancer has grown back, or actually, there are certain situations where patients, for example, may not undergo a hysterectomy. 

And, there are unique cases and those situations where patients are still trying to preserve their fertility, and therefore not wanting to undergo a hysterectomy, or they’re unable to undergo surgery safely. And so, in some unique situations, we may also use hormonal therapy as the mechanism to treat their cancer, and whether that is by way of a pill, whether that is by way of a progesterone intrauterine device, IUD, that is placed into the uterus, we also have situations where we tailor the therapy to the condition of the patient. 

Katherine:

How are patients monitored for a recurrence, and are there approaches to help prevent a recurrence? 

Dr. Ko:

Sure, absolutely. Great question. It is important to continue monitoring patients, even after they’ve gone through treatment. So, I think of it as a multifaceted approach. Usually, it includes office visits, including a physical exam. It includes a thorough intake of all of their symptoms. 

It also includes – depending on the scenario – in some circumstances, regular imaging studies, such as a CT scan or MRI, and sometimes, we also do things like PET scans, and I think that does have to be tailored to the unique patient’s endometrial cancer, unique case, stage, histology, and we kind of tailor which tests we choose to do. The interval of monitoring can vary, so I would say generally speaking, it could be anywhere from three- to six-month visits, and with potentially added scans, as we talked about, and sometimes, we also do certain blood tests in certain cases where we may choose to follow a CA125 blood tumor marker. 

But, I would say that there are different, definitely variants to how we choose to monitor, and there are certain resources we tend to use, such as the NCCN guidelines that providers may reference, and sometimes may even share with the patients to explain why and how we choose to do the monitoring. 

Katherine:

When treating more advanced endometrial cancer disease in general, are the treatment options different than if you were treating somebody who had stage I or stage II, for instance? 

Dr. Ko:

Sure, great question. So, for some patients with, say, stage I, surgery alone is enough. 

For some other patients, subcategories of stage I, where we call them more high/intermediate-risk patients, they’re stage I, but there are a few features about their pathology that might make them slightly higher risk for recurrence – in those cases, we might consider a little bit of radiation after surgery, what we call adjuvant radiation or what we call radiation vaginal brachytherapy. Just three short treatments of a little bit of radiation to the top of the vagina has been shown to possibly decrease chance of recurrence in that area with very minimal side effects. 

So, that would be more commonly in line with stage I. There are some subtypes that can still be what we call high-risk, even in stage I/stage II uterine serous carcinoma, uterine carcinosarcoma. In those cases, we might also recommend chemotherapy along with some vaginal brachytherapy following their hysterectomy, so that’s the early stage. 

And then, with the advanced stage, yes. So, frequently, it’d be surgery first to secure the diagnosis, followed by some type of – it might be primarily chemotherapy, or it could be combination chemotherapy with radiation. And over time, I would say our paradigm for what we use for chemotherapy and radiation has changed a little bit. 

If you go back a couple decades, I think radiation was used a lot – whole pelvic radiation, even just without any chemotherapy. And then, we then had more data from research clinical trials, GOG-258 or PORTEC-3, that then had given us evidence that perhaps doing chemotherapy with some combination of radiation is going to be beneficial, or even moving towards primarily radiation could be a very good option in terms of long-term benefit/long-term survival. 

And, of course, that brings us to the present day, those two trials that I mentioned from ASCO, the GY018 and the RUBY, now bringing in the immunotherapy component to the chemotherapy, so there has definitely been an evolution to managing advanced stage. 

Katherine:

Yes. Dr. Ko, what goes into determining a treatment approach for an individual patient? Is there key testing that helps guide a patient’s prognosis and treatment options? 

Dr. Ko:

Absolutely. So, I think the key pieces of information come from several sources. First, we do take the whole patient into account, like baseline health, baseline function, meaning every day, how active are you? Are there limitations to your daily activities? Looking at baseline health conditions, what we call comorbidities. Are there other health conditions, like diabetes, heart conditions, lung condition, kidney conditions, that could really impact a patient’s overall health and wellbeing? That is always part of it, number one. 

Then, we look specific to the cancer details. So, from all the pathology information, biopsies, followed by a surgical staging procedure, what exact stage, what exact substage, and we might even look at other unique features. Was there cells that got into the lymph vessels, the lymph nodes? Are there other just features from a pathology standpoint that are important, like the – I talked about microsatellite status, microsatellite instable versus microsatellite stable. 

Those are all information we can gather from the tumor tissue itself. That then kind of tailors our therapy. And then, like I was saying, now we’re going into this molecular era where we can actually take that tumor tissue and even do more expanded testing on it. 

So, I think it’s worthwhile to talk to your provider and say, “Hey, would it be worthwhile to send my tumor out for expanded testing, whether it’s done at your institution, at a specialized lab, or whether it’s sent out to a company that does expanded testing?” Because then, they might be able to test for 500 different genetic signatures, a much more broad panel, but that might open the door for opportunities to say, “Hey, you actually do have a very unique signature, and maybe it is worth tailoring your therapy even further.” 

So, I think these are very important questions to have with your provider, and these pieces of information can help guide the prognosis. I think we’re always asking what does this mean long-term, and I think when we have all these individual pieces of information, we can then give guidance on that.  

Katherine:

Well, that leads me into my next question. I wanted to get your point of view on why is it important for patients to engage in their care and their treatment decisions? 

Dr. Ko:

Right. I think that it is so important. Medical treatments, I think, do work the best for the patient when the patient is truly an active participant, and what I mean by that is I think we can really understand the patient if there’s a conversation, there’s a mutual discussion, and I think every patient has unique circumstances, has unique goals, has…whether it’s just the daily whatever responsibilities, or just either health or non-health concerns that they have, we want to be able to find a treatment that fits the patient, and we realize that one treatment doesn’t fit all. 

And so, the more, I think, that there is this mutual discussion, mutual understanding, then there’s a mutual decision treatment plan that is made, and there’s the more ability to modify that plan when – if you realize, oh, maybe we can tailor it, maybe we try one thing, and maybe we realize we got to change a little bit.  

And, I think that with a cancer condition, it is a journey. It is not just a one-time thing. It really is a journey, and I think that the more a patient can participate throughout that journey, I think the better the outcomes for the patient, and honestly, the better the treatment course will be for everyone participating. 

Katherine:

Why should a patient consider finding an endometrial cancer specialist? What are the benefits? 

Dr. Ko:

So, I think naturally, an endometrial cancer specialist is a provider who spends more time thinking about the disease, reading about it, looking at what’s the newest research studies that are coming out, what are the available clinical trials here, locally, regionally, or nationally, what are other support services available for the patient in the space. 

And, of course, probably the folks that do the most surgeries gear towards endometrial cancer patients, and so, I think just working in that space naturally then brings more resources and more opportunity for the patient to kind of really know what’s out there, what is the newest, and I think that really benefits the patient. 

Katherine:

Thank you for sharing all this information. I’d like to close with your thoughts on the future of endometrial cancer care. Are you hopeful? 

Dr. Ko:

Yes. I think that I’m especially hopeful, especially within these last even few years, of where our field is going. I want to say I think there’s so much more that needs to be done.  

I don’t think we’re ready to close the books on endometrial cancer. I think this is just a wonderful opening of a chapter where we’re seeing many more therapies come about. I do think that something that is concerning is that we are seeing more cases of endometrial cancer being diagnosed – yeah, so it is absolutely true. There is very robust data that is collected by our CDC and cancer registry in the country, and it is showing that there is actually a rising incidence, that the number of endometrial cancer cases in this country is actually increasing over time, and it has – 

Katherine:

Why is that? 

Dr. Ko:

It’s a great question. 

Katherine:

Nobody knows – the data doesn’t include that information? 

Dr. Ko:

I think there’s definitely some information, there is definitely information out there. I think some of it – and this is not all of it – I think some of it is related to the increase in obesity and the increase in average weight over time, and this metabolic condition to some degree, I think, does stimulate potential risk for endometrial cancer. 

However, that is not the only reason, and what is concerning is that what we’re seeing is there’s a specific rise in subtypes of endometrial cancer in certain populations, particularly the Black and Hispanic patient populations, and we’re seeing a rise in the most aggressive types of endometrial cancer in those patient populations. I think there’s a lot of research going on right now in that to try to understand why. Is it just because we’re picking it up more? I don’t think that’s the bottom line. 

And, I think what we’re also realizing as we’re studying these various tumor types of endometrial cancer, they are driven by different biology. So, I think to some extent, the ones that are more maybe related to obesity or hormones and all may be slightly different – not completely separate, but that there is underlying different genetic basis for some of these cancers developing, and whether that’s a combination of underlying genes, environment, exposure, or all of the numerous factors, we just know it is happening, and so, it really is critical in my mind that the awareness and the focus and attention on endometrial cancers is really there, that we really think about it, that we share the information as much as possible, and that we can really then come to better – have more opportunity for treatments, be able to diagnose it sooner, be able to have more opportunities to treat it, and honestly, have better survival and outcomes for our patients. 

Katherine:

Dr. Ko, thank you so much for joining us today. You’ve given us so much information. 

Dr. Ko:

Thank you. It was my pleasure. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about endometrial cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell. Thanks for joining us. 

What Do You Need to Know About Emerging Endometrial Cancer Research?

What Do You Need to Know About Emerging Endometrial Cancer Research? from Patient Empowerment Network on Vimeo.

Endometrial cancer treatment and research is evolving quickly. Dr. Emily Ko provides an update on new and emerging approaches, explains how these therapies work to treat endometrial cancer, and shares tips for partnering with your team on key decisions.
 
Dr. Emily Ko is a gynecologic oncologist and Associate Professor of Obstetrics and Gynecology at the University of Pennsylvania. Learn more about Dr. Ko.

Related Programs:

What Endometrial Cancer Patients Should Know About Clinical Trials

Endometrial Cancer Treatment Options for Patients to Consider

Endometrial Cancer Treatment Options for Patients to Consider

Emerging Endometrial Cancer Treatments _ Promising Data and Challenges

Emerging Endometrial Cancer Treatments | Promising Data and Challenges


Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. Today’s program focuses on helping patients with endometrial cancer learn more about evolving research and treatments. We’re also going to discuss how patients can collaborate with their team on care decisions. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar. 

At the end of the program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Emily Ko. Dr. Ko, welcome. Would you please introduce yourself? 

Dr. Ko:

Surely. Thank you so much. My name is Dr. Emily Ko, and I am a gynecologic oncologist. Currently, I’m an associate professor at the University of Pennsylvania, and as part of my daily work, I see patients, I provide surgical and medical treatments for gynecologic cancers, and I also am a researcher involved particularly in endometrial cancer. 

Katherine:

Thank you so much for taking the time out of your schedule to join us today. 

Dr. Ko:

Thank you. 

Katherine:

Well, let’s start by learning about the latest research news. Just this June, endometrial cancer researchers from around the world met to discuss their findings at the annual American Society of Clinical Oncology meeting, or ASCO, in Chicago. Can you walk us through the highlights that patients should know about? 

Dr. Ko:

Sure. So, the ASCO meeting is a very big meeting that happens once a year in June, and really, it is a national – actually, international – meeting where the biggest breakthroughs in cancer therapy are really presented and discussed. 

So, within the field of gynecologic cancer and specifically endometrial cancer, we really saw a couple breakthrough clinical trial results, if you will. The two specific trials that have hit the spotlight – and, it was presented at ASCO; they were also previously presented at the Society of Gynecologic Oncology annual meeting in March of 2023. These two trials – one of them is called GY018, and the other one is called RUBY, and these two trials specifically were geared at patients with endometrial cancer of either advanced stage, meaning stage III or IV at diagnosis, or patients who have recurrent endometrial cancer.  

And, these both trials were very large, multisite, international trials enrolling a huge number of patients. They were randomized controlled trials, meaning that they were specifically testing what we call a standard therapy, Taxol-carboplatin, versus a standard therapy plus a newer agent, and that newer agent falls in the realm of an immunotherapy drug. 

So, with this kind of novel approach, where we’re combining standardly used chemotherapy plus a newer immunotherapy drug, the question was if you did this combination, would patients have a better outcome? And, in fact, the groundbreaking news was that yes, patients did have a better outcome with this new combination of therapy, and this was shown in various forms of results. 

One of the primary outcomes is always something called survival, and with the GY018, they looked at progression-free survival as a primary outcome, and it did show that patients on this new combination did better with progression-free survival. And the difference was about median of about three months. Now, that may not sound like a whole lot. However, in the realm of cancer therapy, when you take a very large group of patients, that was a meaningful difference that was statistically significant. 

And furthermore, as we’re moving forward with our therapy drugs, we are moving into this era of targeted therapy, precision medicine, where we’re really trying to hone into more the specifics of the biology of each person’s cancer, and not treating everyone the same. 

What’s interesting with these two trials is when they looked at different subpopulations of patients with advanced or recurrent endometrial cancer, whether they had a type of endometrial cancer that was considered MSI-high, or a microsatellite instable type of cancer, which basically refers to a certain biology of these endometrial cancers, it has to deal with how the cells – the cancer cells – behave, how they’re able to not follow the rules and be able to replicate themselves. 

The patients who are MSI-high particularly had a really great response with this chemotherapy, so it was even beyond just a three-month difference. With that being said, even in patients who are what we call microsatellite-stable, who didn’t have this unique signature, they still saw a benefit with this novel combination, and to add to that, the nice thing about it is the toxicities were not bad. Even this new combination was very well-tolerated. 

It was not a high rate of severe toxicities or side effects, if you will, and that actually, the great majority of patients were able to stay on this therapy and really get through – complete the therapy course. 

So, there are some sort of nuanced differences between the two trials I mentioned, GY018 versus the RUBY. And some of those details are with regards to the even specific subtype of endometrial cancer, which we haven’t talked about yet, for example, uterine carcinosarcoma versus uterine serous carcinoma, uterine clear cell, uterine endometrioid – these are all specific subtypes of endometrial cancer. So there are some nuances where the RUBY trial was able to include patients with uterine carcinosarcoma, whereas the GY018 did not. 

But suffice it to say, now we have enough data that virtually all endometrial cancer patients with advanced stage, regardless of what histology, there is essentially a trial that can apply to you where it demonstrated this added benefit to doing this novel combination, and that was found with microsatellite-stable patients as well as microsatellite-instable in both randomized controlled trials that I mentioned. 

Katherine:

Such exciting news! That’s great! Well, beyond ASCO, Dr. Ko, are there other research or treatment advances that patients should know about?  

Dr. Ko:

Certainly. Like I mentioned, we’re really moving towards the realm of treating with a targeted therapy approach, and within endometrial cancer, the prior paradigm was much simpler, but really not in the space of target therapy. So, for example, what does that mean? 

So, as we’re realizing that there are very unique biologic signatures to different patients’ endometrial cancer – there could be, for example, some cancers that are particularly receptive to hormonal therapy, meaning their specific cancer, when we send it for detailed – we call it genomic or somatic testing, we can discover, oh, they have estrogen-receptor-positive, progesterone-receptor-positive, and so, those type of cancers may be very responsive to hormonal-based therapy, and in that space, we have a standard available drugs, but we also have clinical trials that are trying newer drugs. 

If, for example, the standard aromatase inhibitor or the standard progesterone agent may be helpful, but there are even more in that space that this point – CDK inhibitors that you can combine with these aromatase inhibitors or hormonal agents that have been around for longer that have shown a lot of promise, a lot of data in breast cancer. But now we’re realizing, wow, there could be some efficacy in endometrial cancer as well, so that’s just one example. 

And there’s other unique biologic gene signatures, again, kind of a good list now out there, that are being studied in various clinical trials, whether they’re PARP inhibitors, whether they’re drugs that target CCNE1, whether they’re drugs that target ARID1A, so there are actually many more that are available. So, they’re really expanding the opportunity for treatment for endometrial cancer patients. 

Katherine:

Well, you just mentioned clinical trials, and I think it’s a good topic to cover a little bit. Why is it important for patients to actually consider enrolling? What are the benefits for them? 

Dr. Ko:

Sure.

So, while we certainly have a good armamentarium of standard-of-care therapies already, and I should mention that does include our classic chemotherapy drugs like paclitaxel (Abraxane), carboplatin (Paraplatin), and even doxorubicin (Adriamycin), if you will, or doxorubicin Hcl (Doxil), there are the immunotherapy drugs now that have become standard of care as well, like pembrolizumab (Keytruda), but sometimes, despite using those best available drugs, the cancer unfortunately either continues to grow or you had a good response, but somehow it shows up again – the cancer shows up again – and so, then, we’re looking for additional opportunities, additional therapies. 

And so, some of the best opportunities are actually to consider these clinical trials. The way that clinical trials are designed is that they always are going  to provide you at least a backbone of a standard available therapy, so you’re never going to get less than what would be considered standard of care. 

But, what they’re doing is they’re usually partnering another drug – a more novel therapy – or they’re basically testing a more novel therapy that could be more targeted, that could potentially have better efficacy than what’s already available standardly. And so, the value of that is that you could have an opportunity to have a therapy that could work even better.  

When you’ve tried something already, unfortunately, the cancer has grown, there is still opportunity, and while you’re on a clinical trial, I think one of the huge benefits is it’s very regulated. You are monitored so closely because at the base of all of this is safety. There is never going to be a drug or therapy that’s going to be administered to a patient without ensuring that there’s absolute safety for that patient, and so, that’s a way that you really have opportunity to get more treatment that could really help your cancer condition and do it in a very, very safe, formal fashion. 

Katherine:

And ultimately help others as well, in the future.  

Dr. Ko:

Exactly, absolutely, because as you’re participating in this process – and, of course, it’s a voluntary process to participate on a clinical trial, so we so appreciate all the patients who, in the past, have participated and are willing to participate in the future, but allows us also to really gather a lot of information to really inform cancer treatment for all the patients coming down the road, and those could be anyone. They could be our neighbors, our friends, our own family members, and that could really be so helpful to everyone that’s going through this type of thing. 

Katherine:

Absolutely, yeah. I’d like to back up a bit and talk about what endometrial cancer is. It’s often referred to as uterine cancer. So, are they the same thing? Are these terms interchangeable? 

Dr. Ko:

Sure, it’s a great question. So, endometrial cancer refers to cancer that starts in what I call the lining of the uterine cavity. So, inside the uterus, there’s a uterine cavity, and there’s a tissue that coats that cavity, and that’s called the endometrium. So, endometrial cancer is basically when cancer cells start growing from that tissue. And, of course, since that exists in the uterus, of course, it’s considered uterine cancer, and we’re just being a little bit more specific when we say endometrial cancer. But, of course, endometrial cancer is the most common form of uterine cancer by far, so in some ways, it’s almost – it’s synonymous.  

Katherine:

How is endometrial cancer staged? 

Dr. Ko:

So, the most classic, rigorous way to stage endometrial cancer is through a surgical procedure. So, what that usually involves is it does include a hysterectomy, removing the uterus and the cervix, usually also includes removing the fallopian tubes and the ovaries. 

And, at the same time, the surgeon will do a very thorough assessment of the abdominal pelvic cavity, basically looking around all those areas to see if there’s any signs of visible disease, anything they can see that looks like it could be tumor deposits in the abdominal cavity. If anything is seen, those deposits will be removed and biopsied, so that’s part of the staging procedure. 

And additionally, it’s important to try to assess the lymph nodes, typically. So, there are lymph nodes in the pelvic area, and then, higher up along the aortic area, and so, there are different surgical techniques that we can use to basically test or sample some of those lymph nodes, be able to remove them, send them to the pathologist, look under the microscope to see if there are any microscopic cancer cells that have traveled to those lymph nodes. 

So, that is all part of a surgical procedure, and with all the information collected from those tissue samples that are removed from the body and sent to the pathologist, but the pathologist then reviews all of that under a microscope, and then can issue a very thorough report describing where the cancer cells are located, and by definition, where the cancer cells are located then defines what the stage is of the cancer. 

Katherine:

Can you give me an example? 

Dr. Ko:

Of course. So, for example, if the cancer cells are located only in the uterus, and they’re not found anywhere else, then that is a stage I. If the cancer cells have traveled to the cervix area specifically, this we call a cervical stroma, that becomes a stage II. If the cancer cells have, for example, traveled to the fallopian tubes, or the ovaries, or the lymph nodes, then that becomes a stage III, and there are sort of substages within those categories as well. 

Katherine:

But stage III would be the highest or most severe? 

Dr. Ko:

So, there’s stage III, and then there’s actually stage IV. So, if the cancer cells have traveled outside of the pelvis into the abdominal area, then we consider that a stage IV. 

Katherine:

And that would be considered advanced endometrial cancer? 

Dr. Ko:

Right. So, by definition, “advanced” typically refers to stage III or IV. 

Katherine:

I see, okay. Now that we understand more about the disease itself, I’d like to talk about the treatments that are currently available. You mentioned chemotherapy, but what else is available for people? 

Dr. Ko:

Absolutely. So, treatment for endometrial cancer is usually some combination of surgery, and then it may be followed by possibly chemotherapy, as well as radiation, and sometimes, it may be a combination of all three treatments, or sometimes, it’s a combination of one or two of those, depending on the exact stage, depending on the exact cell type, and some of the other factors. 

Katherine:

Are hormonal therapies used as well, and targeted therapies? 

Dr. Ko:

Yes. 

Katherine:

I know they are in other cancers. 

Dr. Ko:

Yes. And so, I think the question is where do those come into play? So, I would say the usual algorithm most commonly would be that surgery is done first, as the most common first step, and then, based on the information obtained from surgery and the pathology report that comes from that, then there’s usually some type of a recommendation about should there be a second stepped treatment, and that frequently can be chemotherapy/radiation.  

Now, the areas where targeted therapy – for example, immunotherapy – where does that come in? So, that now has come into the – I would call it the second stage. We’re combining it with the classic chemotherapy drugs – Taxol-carboplatin, for example. That’s one example where it could come into play. Another example could come into play where a patient had gone through classic Taxol/paclitaxel and carboplatin, then had cancer come back, and so, that could be another instance where that pembrolizumab or pembro with lenvatinib (Lenvima) combination can be used in the setting of recurrence. 

Now, we could also say, hey, if your cancer type has those hormonal receptors present or is some type of what we call endometrioid histology, and we think that hormonal therapy may be more effective in that case, then that could also be used in a setting where the cancer has kind of grown again, the cancer has grown back, or actually, there are certain situations where patients, for example, may not undergo a hysterectomy. 

And, there are unique cases and those situations where patients are still trying to preserve their fertility, and therefore not wanting to undergo a hysterectomy, or they’re unable to undergo surgery safely. And so, in some unique situations, we may also use hormonal therapy as the mechanism to treat their cancer, and whether that is by way of a pill, whether that is by way of a progesterone intrauterine device, IUD, that is placed into the uterus, we also have situations where we tailor the therapy to the condition of the patient. 

Katherine:

How are patients monitored for a recurrence, and are there approaches to help prevent a recurrence? 

Dr. Ko:

Sure, absolutely. Great question. It is important to continue monitoring patients, even after they’ve gone through treatment. So, I think of it as a multifaceted approach. Usually, it includes office visits, including a physical exam. It includes a thorough intake of all of their symptoms. 

It also includes – depending on the scenario – in some circumstances, regular imaging studies, such as a CT scan or MRI, and sometimes, we also do things like PET scans, and I think that does have to be tailored to the unique patient’s endometrial cancer, unique case, stage, histology, and we kind of tailor which tests we choose to do. The interval of monitoring can vary, so I would say generally speaking, it could be anywhere from three- to six-month visits, and with potentially added scans, as we talked about, and sometimes, we also do certain blood tests in certain cases where we may choose to follow a CA125 blood tumor marker. 

But, I would say that there are different, definitely variants to how we choose to monitor, and there are certain resources we tend to use, such as the NCCN guidelines that providers may reference, and sometimes may even share with the patients to explain why and how we choose to do the monitoring. 

Katherine:

When treating more advanced endometrial cancer disease in general, are the treatment options different than if you were treating somebody who had stage I or stage II, for instance? 

Dr. Ko:

Sure, great question. So, for some patients with, say, stage I, surgery alone is enough. 

For some other patients, subcategories of stage I, where we call them more high/intermediate-risk patients, they’re stage I, but there are a few features about their pathology that might make them slightly higher risk for recurrence – in those cases, we might consider a little bit of radiation after surgery, what we call adjuvant radiation or what we call radiation vaginal brachytherapy. Just three short treatments of a little bit of radiation to the top of the vagina has been shown to possibly decrease chance of recurrence in that area with very minimal side effects. 

So, that would be more commonly in line with stage I. There are some subtypes that can still be what we call high-risk, even in stage I/stage II uterine serous carcinoma, uterine carcinosarcoma. In those cases, we might also recommend chemotherapy along with some vaginal brachytherapy following their hysterectomy, so that’s the early stage. 

And then, with the advanced stage, yes. So, frequently, it’d be surgery first to secure the diagnosis, followed by some type of – it might be primarily chemotherapy, or it could be combination chemotherapy with radiation. And over time, I would say our paradigm for what we use for chemotherapy and radiation has changed a little bit. 

If you go back a couple decades, I think radiation was used a lot – whole pelvic radiation, even just without any chemotherapy. And then, we then had more data from research clinical trials, GOG-258 or PORTEC-3, that then had given us evidence that perhaps doing chemotherapy with some combination of radiation is going to be beneficial, or even moving towards primarily radiation could be a very good option in terms of long-term benefit/long-term survival. 

And, of course, that brings us to the present day, those two trials that I mentioned from ASCO, the GY018 and the RUBY, now bringing in the immunotherapy component to the chemotherapy, so there has definitely been an evolution to managing advanced stage. 

Katherine:

Yes. Dr. Ko, what goes into determining a treatment approach for an individual patient? Is there key testing that helps guide a patient’s prognosis and treatment options? 

Dr. Ko:

Absolutely. So, I think the key pieces of information come from several sources. First, we do take the whole patient into account, like baseline health, baseline function, meaning every day, how active are you? Are there limitations to your daily activities? Looking at baseline health conditions, what we call comorbidities. Are there other health conditions, like diabetes, heart conditions, lung condition, kidney conditions, that could really impact a patient’s overall health and wellbeing? That is always part of it, number one. 

Then, we look specific to the cancer details. So, from all the pathology information, biopsies, followed by a surgical staging procedure, what exact stage, what exact substage, and we might even look at other unique features. Was there cells that got into the lymph vessels, the lymph nodes? Are there other just features from a pathology standpoint that are important, like the – I talked about microsatellite status, microsatellite instable versus microsatellite stable. 

Those are all information we can gather from the tumor tissue itself. That then kind of tailors our therapy. And then, like I was saying, now we’re going into this molecular era where we can actually take that tumor tissue and even do more expanded testing on it. 

So, I think it’s worthwhile to talk to your provider and say, “Hey, would it be worthwhile to send my tumor out for expanded testing, whether it’s done at your institution, at a specialized lab, or whether it’s sent out to a company that does expanded testing?” Because then, they might be able to test for 500 different genetic signatures, a much more broad panel, but that might open the door for opportunities to say, “Hey, you actually do have a very unique signature, and maybe it is worth tailoring your therapy even further.” 

So, I think these are very important questions to have with your provider, and these pieces of information can help guide the prognosis. I think we’re always asking what does this mean long-term, and I think when we have all these individual pieces of information, we can then give guidance on that.  

Katherine:

Well, that leads me into my next question. I wanted to get your point of view on why is it important for patients to engage in their care and their treatment decisions? 

Dr. Ko:

Right. I think that it is so important. Medical treatments, I think, do work the best for the patient when the patient is truly an active participant, and what I mean by that is I think we can really understand the patient if there’s a conversation, there’s a mutual discussion, and I think every patient has unique circumstances, has unique goals, has…whether it’s just the daily whatever responsibilities, or just either health or non-health concerns that they have, we want to be able to find a treatment that fits the patient, and we realize that one treatment doesn’t fit all. 

And so, the more, I think, that there is this mutual discussion, mutual understanding, then there’s a mutual decision treatment plan that is made, and there’s the more ability to modify that plan when – if you realize, oh, maybe we can tailor it, maybe we try one thing, and maybe we realize we got to change a little bit.  

And, I think that with a cancer condition, it is a journey. It is not just a one-time thing. It really is a journey, and I think that the more a patient can participate throughout that journey, I think the better the outcomes for the patient, and honestly, the better the treatment course will be for everyone participating. 

Katherine:

Why should a patient consider finding an endometrial cancer specialist? What are the benefits? 

Dr. Ko:

So, I think naturally, an endometrial cancer specialist is a provider who spends more time thinking about the disease, reading about it, looking at what’s the newest research studies that are coming out, what are the available clinical trials here, locally, regionally, or nationally, what are other support services available for the patient in the space. 

And, of course, probably the folks that do the most surgeries gear towards endometrial cancer patients, and so, I think just working in that space naturally then brings more resources and more opportunity for the patient to kind of really know what’s out there, what is the newest, and I think that really benefits the patient. 

Katherine:

Thank you for sharing all this information. I’d like to close with your thoughts on the future of endometrial cancer care. Are you hopeful? 

Dr. Ko:

Yes. I think that I’m especially hopeful, especially within these last even few years, of where our field is going. I want to say I think there’s so much more that needs to be done.  

I don’t think we’re ready to close the books on endometrial cancer. I think this is just a wonderful opening of a chapter where we’re seeing many more therapies come about. I do think that something that is concerning is that we are seeing more cases of endometrial cancer being diagnosed – yeah, so it is absolutely true. There is very robust data that is collected by our CDC and cancer registry in the country, and it is showing that there is actually a rising incidence, that the number of endometrial cancer cases in this country is actually increasing over time, and it has – 

Katherine:

Why is that? 

Dr. Ko:

It’s a great question. 

Katherine:

Nobody knows – the data doesn’t include that information? 

Dr. Ko:

I think there’s definitely some information, there is definitely information out there. I think some of it – and this is not all of it – I think some of it is related to the increase in obesity and the increase in average weight over time, and this metabolic condition to some degree, I think, does stimulate potential risk for endometrial cancer. 

However, that is not the only reason, and what is concerning is that what we’re seeing is there’s a specific rise in subtypes of endometrial cancer in certain populations, particularly the Black and Hispanic patient populations, and we’re seeing a rise in the most aggressive types of endometrial cancer in those patient populations. I think there’s a lot of research going on right now in that to try to understand why. Is it just because we’re picking it up more? I don’t think that’s the bottom line. 

And, I think what we’re also realizing as we’re studying these various tumor types of endometrial cancer, they are driven by different biology. So, I think to some extent, the ones that are more maybe related to obesity or hormones and all may be slightly different – not completely separate, but that there is underlying different genetic basis for some of these cancers developing, and whether that’s a combination of underlying genes, environment, exposure, or all of the numerous factors, we just know it is happening, and so, it really is critical in my mind that the awareness and the focus and attention on endometrial cancers is really there, that we really think about it, that we share the information as much as possible, and that we can really then come to better – have more opportunity for treatments, be able to diagnose it sooner, be able to have more opportunities to treat it, and honestly, have better survival and outcomes for our patients. 

Katherine:

Dr. Ko, thank you so much for joining us today. You’ve given us so much information. 

Dr. Ko:

Thank you. It was my pleasure. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about endometrial cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell. Thanks for joining us.