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What Could Advances in Lung Cancer Research and Treatment Mean for You?

What Could Advances in Lung Cancer Research and Treatment Mean for You? from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Manish Patel discusses how lung cancer treatment approaches have evolved, specifically around targeted therapy and immunotherapy. Dr. Patel also provides advice for learning about and participating in clinical trials.

Dr. Manish Patel is a medical oncologist and Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota. Learn more about Dr. Patel, here.

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Transcript:

 Katherine Banwell:

When it comes to lung cancer research and emerging treatment options, what are you excited about, specifically?

Dr. Patel:

Well, I’m really excited about the fact that in 2021 chemotherapy is really no longer the backbone of treatment. It’s really now become where we are really focusing on whether immunotherapy is the main modality of treatment or if it’s a targeted therapy.

And while we do still have chemotherapy and we use it, it’s not the main focus of our treatment. So, that’s really exciting. I personally am extremely excited about all of the advances in immunotherapy and the new methods that are coming across in new clinical trials to improve upon immune responses in patients with lung cancer.

Katherine Banwell:

When do you think a clinical trial should be considered for lung cancer treatment?

Dr. Patel:

Well, I think that’s a great question. And I think, honestly, it could be considered at any point in the patient’s treatment plan. Now, just to expound on that a little bit further, I think in the setting where a patient should be cured of their lung cancer with the treatment that we propose, we have to be careful that we are putting in adequate safeguards that the trial that we propose ensures that they’re receiving standard of care treatment but maybe something additional to try to improve upon that treatment.

On the other hand, if a patient has a more advanced cancer, then there is little bit more leeway in terms of the things that we can try to do. But of course, we always want to make sure that whatever we offer them, we have a reasonable expectation of working as well or better than the standard of care.

Katherine Banwell:

How can patients stay up to date on research?

Dr. Patel:

I think there are a couple of very useful resources online to stay abreast of things. A particular website that I think is very useful for patients is something called YouAndLungCancer.com.

And that is a fairly expansive portal that is patient-focused and really provides a lot of video tutorials on lung cancer, different treatments at different stages, new treatments that are available. And that’s a site that gets updated fairly regularly in terms of standard of care. And so, as we are in a phase where lung cancer research is really advancing very quickly, and these updates are important that they’re, you know, sort of sharing all of the new things that are coming along in lung cancer. 

Why Should You Ask About Lung Cancer Biomarker Testing?

Why Should You Ask About Lung Cancer Biomarker Testing? from Patient Empowerment Network on Vimeo.

Biomarker testing is a vital component of lung cancer care. Dr. Manish Patel, a lung cancer expert, shares important questions for patients to ask about this essential testing to help ensure optimal care.

Dr. Manish Patel is a medical oncologist and Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota. Learn more about Dr. Patel, here.

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Shared-Decision Making Your Role in Lung Cancer Treatment Choices


Transcript:

 Katherine Banwell:

Why should lung cancer patients ask their doctor about biomarker testing?

Dr. Patel:

It’s extremely important. Biomarker testing is really the guiding principles by which we make a treatment plan for lung cancer patients in 2021.

We know that every patient’s lung cancer is a little bit different at the molecular level. So, they might look the same under the microscope, but, you know, if we get to a more deeper level, we can understand that they are quite different and they may respond differently to different treatments.

And so, it’s extremely important. And I think it’s important to know that nationwide we don’t always do a great job of doing real adequate biomarker testing. And so, from a patient perspective, it’s really useful to be an advocate for yourself and to ask your physician, you know, “Have we done biomarker testing, and to what extent have we done biomarker testing?” because it’s not uniform across the country at the moment.

Katherine Banwell:

Are there specific biomarkers that affect treatment choices?

Dr. Patel:

Absolutely there are. So, as an example, the molecular testing with DNA mutation analysis – so we actually look at the mutations that are present within a patient’s tumor, and that really does define a group of patients both in the curative setting and in the setting with more advanced disease that defines our treatment choices. Likewise, PD-L1 is a biomarker now that is being incorporated onto whether or not we use immunotherapy or whether we use immunotherapy with chemotherapy for patients that don’t have mutations.

So, it’s become an extremely important part of our treatment regimen. 

Shared-Decision Making: Your Role in Lung Cancer Treatment Choices

Shared-Decision Making: Your Role in Lung Cancer Treatment Choices from Patient Empowerment Network on Vimeo.

Lung cancer treatment decisions involve various factors, but what role should the patient play when choosing therapy? Lung cancer expert Dr. Manish Patel explains the considerations involved, the concept of shared decision-making when making a treatment choice, and provides questions to ask about a proposed treatment plan.

Dr. Manish Patel is a medical oncologist and Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota. Learn more about Dr. Patel, here.

See More From Engage Lung Cancer

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Why Should You Ask About Lung Cancer Biomarker Testing?


Transcript:

Katherine Banwell:

When making a treatment choice, what three key considerations are there for lung cancer patients?

Dr. Patel:

Well, I think always the first one that’s most important is really the patient in front of me, you know, what their physical function is, what their other medical problems that they might have. Number two is always going to be to consider the stage of the cancer, how advanced the cancer is. And then really with regards to lung cancer these days, we really have to consider what kind of lung cancer it is. And I don’t mean necessarily just differentiating between the kinda major subtypes of lung cancer, but really looking at more detailed understanding of the specific type of lung cancer because it does, sort of, guide our treatment.

Katherine Banwell:

The term “shared decision-making” is being used a lot lately when talking about patient care. What does that term mean to you?

Dr. Patel:

Well, I think what that means is as the oncologist – the treating oncologist – my role is to educate the patient on what the treatment options are, give my recommendations of what I think the best options are for that individual patient.

But really the shared decision-making ultimately means that we have a discussion about what the goals of the patient are and how those match up with what my recommendations are and then come up with a treatment plan that suits both mine and the patient’s needs.

Katherine Banwell:

I know some patients are hesitant to talk to their doctor about questions they may have about how they’re feeling.

Does that come into the shared decision process?

Dr. Patel:

I think it does in some ways. I mean, we do try to explore how much the patient is understanding from what we’re talking about, also make a lot of attempts to understand the concerns or hesitations that a patient might have about what we’re talking about, or perhaps if they are hesitant to talk about certain aspects of their health with us. But we do try to tease that out as much as we can in our patient encounters so we can make really the best decision for that patient.

Katherine Banwell:

Are there questions that patients should consider asking about their proposed treatment plan?

Dr. Patel:

Well, I think it’s always useful for patients to ask, “What can they expect?” You know, we talk a lot about potential side effects – what can happen with the treatments – and oftentimes we’re discussing them in sort of worst-case scenarios.

But I think in some ways it’s sometimes helpful for patients to know what do we expect to happen, why we are discussing the extreme cases – best- and worst-case scenarios – really having an idea of what they should expect from treatment. 

What Do You Need to Know About Metastatic Breast Cancer Genetic Testing?

What Do You Need to Know About Metastatic Breast Cancer Genetic Testing? from Patient Empowerment Network on Vimeo.

Why is it important to ask about metastatic breast cancer genetic testing? Find out how test results could reveal more about YOUR breast cancer and could help determine the most effective treatment approach.

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What Questions Should Metastatic Breast Cancer Patients Ask Before Starting a Treatment Plan?


Transcript:

Why should you ask your doctor about metastatic breast cancer genetic testing?

The National Comprehensive Cancer Network – also known as the NCCN – recommends that every metastatic breast cancer patient undergo genetic testing. The test results can help predict how your cancer may behave and could indicate that one type of treatment is more effective than another.

This testing identifies specific gene mutations, proteins, chromosomal abnormalities, and/or other molecular changes that are unique to YOU and YOUR breast cancer.

There are two main types of genetic tests used in breast cancer:

  • Germline or hereditary genetic testing, which identifies inherited gene mutations in the body. These mutations are present from birth, can be shared among family members and be passed on to subsequent generations.
  • The second is somatic or tumor genetic testing, which identifies markers that are unique to the cancer itself. It is also commonly referred to as genomic testing, biomarker testing, or molecular profiling. Somatic mutations are NOT inherited or passed down from family member to family member.
  • Depending on your history, your doctor may order one–or both–of these types of tests.

So why do the test results matter?

  • If you have specific gene mutations – such as the BRCA1 or BRCA2 inherited gene mutations – it could indicate that a targeted treatment approach may be the most effective option. For example, there are two oral targeted therapies that are approved specifically for use in metastatic patients with BRCA1-positive or BRCA2-positive breast cancer.
  • Results of these tests may also help you to find a clinical trial that may be appropriate for your particular cancer.
  • Additionally, results from germline genetic testing may suggest that close family members should also be tested to determine their risk.

How can you insist on the best breast cancer care?

  • First, always speak up and ask questions. Remember, you have a voice in YOUR breast cancer care.
  • Ask your doctor if you have had–or will receive–genetic testing, including germline and somatic testing.
  • If you have already undergone genetic testing, bring a copy of your results to your current doctor, so they can understand your results and determine whether additional testing is needed.
  • Have a discussion with your healthcare team about the test results – including which markers were detected and how results may impact your care and treatment plan.
  • Ask whether your family members should meet with a genetic counselor or undergo testing to help gauge their risk of developing breast cancer.
  • And, finally, bring a friend or a loved one to your appointments to help you process and recall information.

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

How Will You Know if Your Lung Cancer Treatment Is Working?

How Will You Know if Your Lung Cancer Treatment Is Working? from Patient Empowerment Network on Vimeo.

How do lung cancer experts determine if a treatment approach is working? Expert Dr. Heather Wakelee explains how treatment effectiveness is monitored and what should be analyzed when treatments stop working.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

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Transcript:

Katherine:

We have a question that we received from an audience member earlier. Jeff asks, “How do you know if your lung cancer treatment is working?”

Dr. Wakelee:

So, there are a lot of ways of knowing if treatment is helping. So, the one I rely on the most is, “Does the patient overall feel better?” That is difficult to say exactly how. Sometimes people are having breathing problems; they feel that that’s better. Sometimes their energy’s lower. They feel better. It can be vague. We also use scans. So, we tend to get scans, depending on the treatment we’re giving, every couple of months plus or minus, sometimes, every three months to help track what’s actually going on. But occasionally, there are discrepancies.

So, sometimes, the scan, is it better? Is it not better? Can’t really tell. And then, you’re always taking that, “How does the patient feel?” So, usually, if the scans are better, the patient feels better. It’s easy. Usually if the patient’s feeling worse and the scan looks worse, clear decision. Not a good one, but clearly, we need to do something different. But sometimes, you’re left, and especially this happens with the first scan because you get a scan, it takes a little while, you start the new treatment, then you get the next scan, how much of the changes happened before you started the new one and how much didn’t? So, these can be more challenging conversations, but generally if the patient’s feeling a little bit better, the scan’s unclear, we usually say, “You know, let’s give this treatment a little bit more time.” We also, I think your question was specifically around how do we tell if it’s working, but you also often need to be thinking about, “Well, what’s it doing that’s negative to the person and is that potential, those side effects worth the benefits we are or are not seeing?”

So, it’s kind of all of those things together. It can be a bit complex.

Katherine:

What goes into the decision to change therapies if it becomes necessary?

Dr. Wakelee:

So, when we’re thinking about making a change, the way I always look at it is, is where we are today still okay or not? And, if it’s not, that would be because clearly the cancer’s growing or clearly the side effects are just not tolerable. Then, we decide together with the patient we need to do something different. And, when we think about what do we do next, we look at what have we’ve already done, did it work or not, if not, let’s do something more different. And so, let’s think about something that might be somewhat similar. When we’re dealing with targeted therapies, we have ways to try to figure out what changed in the tumor that made it now resistant or not working with that treatment.

And so, with some of the pill drugs, there’s been a lot of research and understanding how does the tumor change that helps it evade, get away from, be resistant to whatever treatment you’re on.

And then, sometimes, we have other pill drugs that work in that particular setting, not always. With immune therapy, we’re trying to better understand why does the immune therapy stop working?

Sometimes you can add back to it, like, you can add chemotherapy back to immune therapy alone or sometimes you can do radiation with immune therapy to get that response back. Or, add other combinations to it. So, that’s another thing that we’re working on. And then, like I said, if someone hasn’t ever had chemotherapy and the tumor’s become resistant, we’re going to be thinking a lot about chemo because that can play a role against so many different reasons that the cancer might not be responding to whatever treatments someone’s on. And then also, looking at how the patient’s feeling and doing, what their overall what we call “performance status, ” their sort of overall health, and how well do we feel with them that they’re going to be able to tolerate the next treatment because, you’re always having to weigh how much is this likely to help, and how might this harm in finding the right balance. 

What Are the Advantages of Newer Lung Cancer Treatment Approaches?

What Are the Advantages of Newer Lung Cancer Treatment Approaches? from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Heather Wakelee shares insight about how newer treatments, such as targeted therapy and immunotherapy, impact quality of life and patient outcomes.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

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Transcript:

Katherine:

Right. What are the advantages of these new treatment approaches compared to standard chemotherapy?

Dr. Wakelee:

Well, I think the most exciting news that we’ve seen in lung cancer over the last few years is that we’re actually helping more people live longer. And the way that we’re doing that is through these newer treatments. So, when we can personalize treatment by recognizing that a person’s cancer has a specific gene mutation and we can give them the right targeted pill drug, we can help them live longer and feel better because those often have fewer side effects. Wish I could say they were curing the disease, but they’re helping people live longer.

And, that can be measured in years for some folks, which is fantastic. And then, with immune therapy, again, they’re not working for everybody, but they were for a large number of patients with lung cancer with non-small cell to help them live longer with their cancer controlled. And so, we’ve actually improved the overall survival rates for lung cancer with these new developments. Where we can make even more of an impact is also by finding more of the cancers earlier, and that’s where cancer screening is so important also. So, by having more choices, chemotherapy can still help a lot of people. Targeted therapies can help probably close to 20, 30, 40 percent of people with non-small cell lung cancer that’s the adenocarcinoma type.

And then, the immune therapies can help other people living with lung cancer. Usually immune therapies don’t work on the same tumors the way the targeted pills work. So, you’re kind of getting at different groups of people with those different strategies. It’s not completely true, but it’s a kind of general principle about it.

Katherine:

What about side effects for some of these treatment choices?

Dr. Wakelee:

So, chemotherapy is one people fear the most, but I think it has a bit more of a bad reputation than it needs. A lot of the lung cancer therapies that are chemotherapy can be reasonably tolerated. I mean, I’m not signing up to go get chemotherapy just because. There definitely are side effects. The biggest one is people get fatigue, get really tired. Though, if they’re feeling horrible because of the cancer, a lot of times people feel dramatically better. But, tiredness, it can impact appetite a little bit, though cancer does that also. There can be nausea, vomiting, but we’re much better at controlling that with the newer drugs. Some cancer therapies cause hair loss, but a lot of our non-small cell lung cancer therapies don’t cause hair loss. So, there are a lot of options there you can talk about with your doctor. And then, when the blood counts are low, there can be risk for infection, low red blood cells with anemia.

So, there are a lot of different things. But in general, chemotherapy is better tolerated than people think it’s going to be because in the movies, they make it look horrendous.

With the pill therapies, again, lots of variability depending on the specific pill. Some of them cause rash. Some don’t. Some of them can cause some changes to the heart that we have to monitor with EKGs, electrocardiograms, some don’t. Some cause some changes to labs like for liver tests that we have to monitor. Some don’t. Some cause hair color changes. Some don’t. It’s always to gray, unfortunately.

So, there are a lot of different variations in what different treatments can do. And so, it’s just really important if your doctor is talking with you about starting one of the targeted pill drugs that you really ask what are the side effects I need to be watching for, what are the ones I need to know to call you about, and which are the ones I just know, “Okay, this is happening and it’s okay. It’s going to cause swelling in the ankles,” no, just a huge range of them. And then, with the immune therapy drugs, they tend to be mostly fatigue, just like with chemotherapy, though some people feel fine.

What we have to watch for is that they can cause what we call autoimmunity. So, it’s talking about the fact that the way they work is they help the immune system better recognize the cancer, and they do that by taking away one of the stop signals. But that stop signal, the PD-1, PD-L1, that stop signal is also used by a lot of normal cells to tell the immune system to back off.

So, when you remove it, when you block it, the immune system can get confused and start to attack normal cells. So, you can get a rash, people can end up with gut symptoms like diarrhea, they also can end up with it attacking the lungs and causing what we call a pneumonitis lung inflammation or brain symptoms, so, almost anything. Now, those are rare, and we can treat them with steroids. But, people need to be aware that if something new is happening, they need to alert their doctor. I think sometimes, there’s this false impression that immune therapy is completely safe, but, it’s not. And, all of the treatments that I’m talking about are designed to help people live better and live longer when they’re dealing with lung cancer, but they all also have risk.

And so, it’s just really important to have those discussions with the care team as you’re starting something new about what are the things I need to be watching for and to know how to reach people if you’ve got a new and concerning symptom, especially if you’re starting on something new. 

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care? from Patient Empowerment Network on Vimeo.

Expert Dr. Heather Wakelee explains how targeted therapy and immunotherapy work to treat lung cancer and which patient type each therapy is most appropriate for.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

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Transcript:

Katherine:

Dr. Wakelee, you mentioned targeted therapies. How do they work?

Dr. Wakelee:

Targeted therapies are something we can use when we find a specific gene mutation in the tumor. So, I mentioned before that in order for a cancer cell to become cancer, something has to happen to the DNA in the cell.

And, there’s a change or a mutation in the DNA of the cell which leads it to be a cancer. And, a lot of the time, that mutation happens in a specific kind of gene that makes a type of protein called a tyrosine kinase. And for those of you who haven’t studied a lot of science, it’s a word you might not have heard before. But basically, these tyrosine kinases are proteins in the body that make a lot of changes to what’s going on in the rest of the cell. So, they’re sort of what we call regulators. And, one way of thinking about them is like on and off switches. So, normally, their job is to sit and if the right molecule comes around, that turns it on, and then it turns on other proteins in the cell. And if that molecule isn’t there, it’s turned off. So, it’s this on and off switch that does a lot of other aspects of what’s going on in the cell. But, sometimes, a mutation happens. It turns it on all the time. So, it’s like if you leave the light on.

It’s on all the time, that’s using a lot of energy, and that’s actually what’s driving the cell to act like a cancer. And so, we can now look for some of those mutations that turn some of these tyrosine kinases on all the time. But we’ve also developed drugs that we can use to turn them off. So, if we find this specific gene mutation that’s turning, say, the EGFR protein on all the time, if we find that, we can have the patient take a pill that then turns that off.

And that helps the cancer slow down, some of it die, some of the cancer cells die, but it doesn’t completely wipe it out. It helps the patient for a long time though by shrinking the cancer, helping them feel better because the symptoms are gone, keeping the cancer from growing. But, cancer cells are clever. They continue to divide, they can continue to make new mutations, and eventually, they figure out ways around that. So, when we talk about targeted therapy, it’s a setting where we find the cancer.

In the cancer, we find the gene mutation, it’s in one of these specific types of proteins, genes that make specific protein that turn something on that we can then turn off, and with those pill drugs, we can have a big impact for people.

Katherine:

And, what exactly is immunotherapy?

Dr. Wakelee:

Immunotherapies are treatments that were used to help keep the immune system more active.

So, the immune system is a very complex mechanism. There are cells that their whole job is to figure out and find things that are not us. So, they are looking for bacteria, they’re looking for cells that have a virus in them, and when they find it, they attack. And, that attack can be in the form of antibodies, it can be cells that actually go in and attack other cells directly, and we are all familiar a little bit with the immune system because we know that if we get a cold, our body, we can get a fever, that’s part of our immune response, and we get better. And then, some people know the bad side of the immune system if they have allergies or certain autoimmune diseases where the immune system gets a little bit too revved up and starts to recognize normal things as foreign.

So, in the setting of cancer, normally, the immune system is able to recognize a cancer cell, see that it’s different from the rest, and get rid of it. But, cancer cells are clever and they figure out ways to evade the immune system. And, one of the ways they do this is they put a protein called PD-L1. So, PD-L1 is a protein that a lot of our normal cells use to say, “Just a normal cell. Ignore me.”

And so, when an immune cell comes in and sees that, it gets turned off it goes away. So, what our immune therapies do is most of them are blocking that PD-L1 protein. And, when they do that, it’s sort of like taking away the stop sign. So, you’ve got a tumor using a stop sign to say, “Go away, immune cell,” you block it so the immune cells can’t see that stop sign, and so then it kills the cancer cell better. So, that’s how these drugs work, and that’s the immune therapy.

There are some other stop signs besides PD-1 and PD-L1, but that’s the most common. So, when we’re talking about immune therapy, it’s drugs that block that. So, they increase the ability for the immune cell to recognize cancers. The risk from them is that you can get the body to recognize normal tissue as a problem sometimes. So, that’s the toxicity that we watch for. 

What Are the Goals of Lung Cancer Treatment?

What Are the Goals of Lung Cancer Treatment? from Patient Empowerment Network on Vimeo.

The goals of lung cancer treatment can vary depending on the stage. Expert Dr. Heather Wakelee explains how lung cancer stage is determined and shares insight about the goals of treatment at each stage.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

See More From INSIST! Lung Cancer

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Transcript:

Katherine:

Let’s turn to treatment, Dr. Wakelee. On a basic level, what are the goals of treatment for lung cancer?

Dr. Wakelee:

So, with lung cancer, we’d love to cure everybody, that’s the ultimate goal, and do it in a way where people are able to continue living their life as they were before the cancer diagnosis. The ways that we do it, first of all, we’ve got to find the cancer, and that’s where screening is such an important aspect of things. If we can find the cancer at an earlier stage, we’re more likely to be able to cure someone.

So, what do I mean by “earlier stage?” Well, when a tumor first develops, usually, there is a single cell that develops a mutation, meaning a change in the gene, which gives that cell an advantage so it doesn’t die the way it’s supposed to. And then, it keeps growing, and dividing, and making new cells. And those over time get to a large enough size that they are the cancer. And given more time, those cancer cells start to spread into other parts of the body, usually first into what we call the lymph nodes, and from there then into other organs in the body. And this stage refers to health or how the cancer spread. So, the stage I cancer is still in that ball of cancer. Stage II means that it’s spread into some lymph nodes. Stage III is it spread into more lymph nodes, usually in the center part of the chest or mediastinum, and that’s where it starts to be much more difficult for the surgeons to be able to truly remove all of the cancer.

And then stage IV means that the cancer is not something that we’re going to be able to remove with surgery. It’s spread either within the lung to the lining of the lung or it has spread to other organs in the body. And so, when we talk about those stages that I, II, III, IV, it’s a bit more complicated than that. But, I think for most people, if they just think about it as stage I, just the cancer, stage II, lymph nodes and the lungs, stage III, lymph nodes in the center, and then stage IV, elsewhere, that’s a good way to kind of wrap your head around it.

And when we talk about stage I and II, that’s the truly early stage where we hope to be able to cure people with surgery. Surgery alone is enough for the majority of people with stage I cancer, and for maybe half, a little more than half of people with stage II. So, how can we be better than that? Well, that’s where there’s been a lot of new advances. So, adding chemotherapy after surgery can help a lot of stage II patients.

If the tumor genomic testing biomarkers shows that there’s a mutation called EGFR, we now know that there’s a pill drug that people can take that would prolong the time to when the cancer might come back. And then, just very recently, there was stated that that immune therapy drugs

IV can also prolong time to when the cancer comes back and maybe improve cure if the tumor has that biomarker called PD-L1. So, that’s that early stage. So it’s, again, getting more and more complicated and emphasizing that you’ve got to understand the biomarkers of the tumor to know how to best help someone.

When we move to stage III, some have surgery, but when you can’t have surgery, then we do the chemotherapy and the radiation. That’s the key part of the treatment there. And, we also know that immune therapy can be really helpful for a lot of patients when it’s given after the chemo and radiation’s completed. And then for stage IV, I talked about that already, which is you’ve gotta do the biomarkers to figure out the best treatments for some people starting with a targeted pill drug is the right thing if their tumor has those right gene mutations.

For other people, immune therapy alone might be an option if the PD-L1 level is very high and they don’t have one of those gene mutations in the tumor. And for a lot of people, chemotherapy or chemotherapy plus immunotherapy is the right strategy.

Katherine:

Would you help the audience understand the types of therapy for small cell lung cancer specifically?

Dr. Wakelee:

Yes. So, small cell still has the same kind of staging, but it’s a little bit more simple. We talk about extensive stage or limited stage. And what that has to do with is we rarely do surgery for small cell. It tends to have spread earlier. There are a few cases where that’s done, but normally, we divide it up into limited or extensive. And when we talk about that, limited is the radiation doctors can get all of the cancer in one radiation field, and then radiation plus chemotherapy is the standard approach to try to cure. If it’s more extensive than that, then it becomes extensive stage.

And, the best treatment are going to be chemotherapy plus those immune therapy drugs added together.

And so, the chemotherapy drugs that we use for non-small cell and small cell, the platinum drugs play a role in all of it. The drug we partner is a little bit different. There’s a drug etoposide we use a lot in small cell and a lot of other options for non-small cell. And then, the immune therapy drugs, there are a lot of options that are fairly similar for both small cell and for non-small cell. 

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment from Patient Empowerment Network on Vimeo.

How is in-depth lung cancer testing used in determining lung cancer prognosis and treatment? Expert Dr. Heather Wakelee shares insight about biomarker testing, genomic testing, and how test results may impact treatment options.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

See More From INSIST! Lung Cancer

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Transcript:

Katherine:

Dr. Wakelee, but what is genomic or biomarker testing?

Dr. Wakelee:

So, we are struggling with how to have one unifying way of describing it because it’s so complicated. So, to me, biomarker testing is any aspect of the tumor that helps us choose the best treatment for that patient. And so, it’s a very broad term. And, within biomarker testing, there are several different ways that we look at it.

So, one is to look at what proteins are on the cell’s surface. And, we do that by having stains that we use to stain the tissue. So again, complicated, but when a piece of tissue is taken out of the person, part of the tumor is removed. It’s sliced into little tiny slices, which are then put on glass slides that can be looked at under the microscope. And, that’s how the pathology doctors can look and see, “Ah, this looks like cancer,” or, “It doesn’t look like cancer.” When it does look like cancer, you can then put on stains, so basically, different colored antibodies that will light up if that particular protein is there. And so, that helps us figure out for sure that this started in the lung because there are specific proteins that are only found in lung. So, that’s one way we used it, and this is an older technology. But we also can use that to look for how much of this PD-L1 protein is expressed.

And so, that’s an important biomarker, but it’s not based on genomics, which is when we’re talking about the DNA.

Then, we have the genomic testing, and that’s when we’re looking at the genome of the tumor and how that genome is different. And, that’s that DNA or RNA testing. We talk about it with the next-gen sequencing. So, “sequencing,” any of those terms are all meaning we’re looking at some aspect of what makes the tumor genes and therefore the proteins made by the tumor different than the rest of the genes in the person.

And so, that testing, that genomic testing can be done on either the tumor specimen or that’s where we can do blood tests that will be able to pull out those bits of the DNA that are from the tumor versus from the person and help us figure out what’s going on with the cancer. So, when we talk about biomarkers, the whole picture, and when I’m talking with patients who are diagnosed with lung cancer, we talk about well, there’s chemotherapy treatment, which is good for almost everybody. There is targeted therapy.

Targeted therapy is usually based on those genomic tests, and the genomic tests can be done either on the tissue or on blood. But, they’re really important to have a full understanding of the

tumors to do a comprehensive or next-gen sequencing analysis of the tumor or DNA. And then, you have the immune therapy where that PD-L1 biomarker is important. So, that’s the way I think about it, and the biomarkers are really critical for helping us figure out what’s the best path forward for any individual patient.

When I started treating lung cancer patients 20 years ago, we only had chemotherapy. And now, for metastatic disease, with using the right biomarkers, we can figure out so much more about the cancer to be able to personalize the treatment, for many patients, being able to offer pill therapies that are somewhat less toxic and highly active and give people more time. And now, we’re in the immune therapy revolution, which is helping a whole other group of patients living with lung cancer to be able to live with quality life for much longer. And the pace of discovery is just going up so quickly. And, I think that’s what I’m most hopeful about is just how much attention is being paid on lung cancer and finding better therapies that are going to help more people for a longer period of time. 

Which Tests Do You Need Following a Lung Cancer Diagnosis?

Which Tests Do You Need Following a Lung Cancer Diagnosis? from Patient Empowerment Network on Vimeo.

Which lung cancer tests do patients need after a diagnosis? Expert Dr. Heather Wakelee provides an overview of lung cancer testing, explains how the results are used, and discusses how testing differs for small cell lung cancer versus non-small cell lung cancer.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

See More From INSIST! Lung Cancer

Related Resources:

Accessing Personalized Treatment for Lung Cancer

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment


Transcript:

Katherine:

Can you provide an overview of important tests following a lung cancer diagnosis?

Dr. Wakelee:

That’s a fabulous question. When we think about the tests that we need to have done, they’re mostly tests that are done on the tumor, so, either if someone has a surgery or at the time of biopsy. and, that’s where we can figure out what we call, again, the histology that’s squamous or non-squamous. That’s when they look at it under the microscope. But, they also, with the tumor specimen, you can pull the DNA out of the tumor and then test for the gene mutations in the tumor. And, I always emphasize these are not changes in the genes that are in the whole person. They are things that are unique to the tumor. They are what make the tumor different from the rest of the person.

So, we look at those gene mutations, or that’s kind of a biomarker. So, there are a lot of terms that we use, and I know it gets really confusing. So, I try to use “biomarker” to mean all of these things, but that gene mutation is what we look at in the tumor tissue to see if there are specific changes that will allow us to give a pill therapy, a targeted pill therapy. And then, there are also aspects of the tumor that help us figure out whether or not the immune therapy might work, and most commonly, that’s something called PD-L1. That’s a protein that we look at on the surface of the tumor, and so again, under the microscope.

Katherine:

And, when you talk about extracting DNA, is that via a blood test?

Dr. Wakelee:

So, we have two different ways to do that. So, what I was talking about before was from the tumor tissue, you can extract the DNA. But now, there are these liquid biopsies where we can draw blood and find the tumor DNA that is different from the rest of the person’s DNA and look for those gene mutations in the tumor.

And that is where there’s a lot of developments happening. And, that’s so fabulous because they’re often faster results for patients, and it means that you cannot have to go through another biopsy. We still need the biopsy to establish whether or not there is even cancer. But, once we know that there’s cancer for sure, then we can use the liquid biopsies to get a faster information result on those gene mutations and to follow over time to see how the tumor evolves because tumors change after they’ve been treated.

Katherine:

Do you use imaging at all?

Dr. Wakelee:

Yes. Always. So, when someone is first diagnosed with cancer, we usually find that because of imaging, so, a CT scan or an X-ray, maybe they had a screening CT scan or maybe they had a cough that led someone to go get an X-ray, an examination. So, the imaging is a part of the original diagnosis. And in addition to CT scans, we’ll often get a PET scan that helps us look for, in a different way, the rest of the body, maybe an MRI of the brain to look in that area.

And then, wherever we’ve found the tumor, we will track that area with scans over time. And, it gets a little complicated for a patient that was found with what we call early-stage disease. So, stage I or II. Many of the times, those patients can have surgery and then we don’t have any tumor we can follow anymore. But we get CT scans to look to see if it could have come back. For patients with more advanced disease, so, stage III that couldn’t have surgery or stage IV, there we have areas that we’re going to continue to follow with the scans. And which scans and how often is going to depend a lot on what treatment the patient’s on and where the tumors are located that we’re tracking.

Katherine:

Do these tests differ for small cell lung cancer and non-small cell lung cancer patients? And, I know that non-small cell lung cancer is also known as NSCLC.

Dr. Wakelee:

Yes. So, long ago, the only distinction we had with lung cancer was that small cell versus non-small cell, and that is something that is seen under the microscope when that tissue is taken out from the biopsy. The pathology doctors look at it under the microscope, and the cells look different. And, the small cell lung cancer, those cells are small. It’s not very creative naming. And then, everything else is non-small cell or NSCLC. So, it’s SCLC and NSCLC. So, that was one of the first distinctions.

And, it is still very important because the chemotherapy drugs that we use are slightly different. And, the genetic, those gene mutations, we see them in any cancer. That’s what makes a cancer different from the rest of the body. But in small cell lung cancer, the tumor mutations that we see are not things that we know how to target specifically. In non-small cell, there are targets that we can target specifically for some patients.

So, just there, it’s different in having the targeted pill drugs in non-small cell, not so much in small cell. With immune therapy, those newer immune therapy IV drugs, they can work in both small cell and non-small cell.

But for small cell, the biomarkers, that PD-L1 level is not as important for helping us figure out who’s going to benefit. For non-small cell, with many of the drugs, it is important. So, there are differences there. 

Accessing Personalized Treatment for Lung Cancer

 

Accessing Personalized Treatment for Lung Cancer from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Heather Wakelee defines personalized medicine and explains the factors that are considered when determining a treatment approach.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

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Which Tests Do You Need Following a Lung Cancer Diagnosis?

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Transcript:

Katherine:

We’ve been hearing the term “personalized medicine” a lot more often. How would you define that term?

Dr. Wakelee:

That’s a great question. So, I think back when I first started taking care of patients living with lung cancer 20 years ago, we really just had chemotherapy for those with metastatic disease. And for those with earlier stage disease, it was just surgery radiation. And since that time, we’ve learned a whole lot and brought in a lot of different types of treatment. Surgery and radiation still have important roles for many patients.

And we think about them as being targeted and personalized based on stage, but it’s a little bit different. When we talk about personalized, we’re thinking more about what are aspects about the tumor that allow us to pick the right systemic treatment. So, “systemic” meaning a pill or something that we give IV.

With chemotherapy, we don’t have much to pick between them as far as specifics for the tumor. We can look at what we call the histology, which is how it looks under the microscope, whether it’s the squamous type or the non-squamous type and some of the chemotherapy drugs matter there. But, in the last 15, 20 years, we’ve learned about the specific what we call “gene mutations” that define the tumor.

And, depending on the gene mutation in the tumor, for some patients, we can give them pill therapy drugs that will work well. So, that’s personalized. Or, immune therapy now is an option for a lot of patients. That’s usually IV therapy.

And, there are some aspects of the tumor that can help us pick that also. 

Which Lung Cancer Treatment Is Right for You? What You Need to Know

 

Which Lung Cancer Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What do you need to know before deciding which treatment is best for YOUR lung cancer? Lung cancer specialist Dr. Heather Wakelee reviews key factors that help guide treatment decisions, including biomarker testing, and shares advice for partnering with your team to advocate for the best care.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

This program is brought to you by the Patient Empowerment Network. It is made possible through support from Daiichi Sankyo, Foundation Medicine, Illumina, Merck, Novartis, and generous donations from people like you.

See More From INSIST! Lung Cancer

Download Guide

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Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for you today’s program. Today, we’re going to discuss how to access the most personalized lung cancer therapy for your individual disease and why patients should insist on essential testing. 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.

Let’s meet our guest today. Joining me is Dr. Heather Wakelee. Dr. Wakelee, would you please introduce yourself?

Dr. Wakelee:              

Sure. Thank you so much and I’m really delighted to be on this and get to address all of our listeners. So, I am Dr. Heather Wakelee and I am a lung cancer specialist. I work at Stanford University where I’m also the chief of the Division of Medical Oncology.

Katherine:                  

Excellent. Thank you. Before we get into an in-depth discussion on lung cancer treatment, we’ve been hearing the term “personalized medicine” a lot more often. How would you define that term?

Dr. Wakelee:              

That’s a great question. So, I think back when I first started taking care of patients living with lung cancer 20 years ago, we really just had chemotherapy for those with metastatic disease. And for those with earlier stage disease, it was just surgery radiation. And since that time, we’ve learned a whole lot and brought in a lot of different types of treatment. Surgery and radiation still have important roles for many patients.

And we think about them as being targeted and personalized based on stage, but it’s a little bit different. When we talk about personalized, we’re thinking more about what are aspects about the tumor that allow us to pick the right systemic treatment. So, “systemic” meaning a pill or something that we give IV.

With chemotherapy, we don’t have much to pick between them as far as specifics for the tumor. We can look at what we call the histology, which is how it looks under the microscope, whether it’s the squamous type or the non-squamous type and some of the chemotherapy drugs matter there. But, in the last 15, 20 years, we’ve learned about the specific what we call “gene mutations” that define the tumor.

And, depending on the gene mutation in the tumor, for some patients, we can give them pill therapy drugs that will work well. So, that’s personalized. Or, immune therapy now is an option for a lot of patients. That’s usually IV therapy.

And, there are some aspects of the tumor that can help us pick that also.

Katherine:                  

Well, I imagine that much of personalized immunotherapy for a patient requires a number of tests and then a thorough review of the results. So, can you provide an overview of important tests following a lung cancer diagnosis?

Dr. Wakelee:              

That’s a fabulous question. When we think about the tests that we need to have done, they’re mostly tests that are done on the tumor, so, either if someone has a surgery or at the time of biopsy. and, that’s where we can figure out what we call, again, the histology that’s squamous or non-squamous. That’s when they look at it under the microscope. But, they also, with the tumor specimen, you can pull the DNA out of the tumor and then test for the gene mutations in the tumor. And, I always emphasize these are not changes in the genes that are in the whole person. They are things that are unique to the tumor. They are what make the tumor different from the rest of the person.

So, we look at those gene mutations or that’s kind of a biomarker. So, there are a lot of terms that we use, and I know it gets really confusing. So, I try to use “biomarker” to mean all of these things, but that gene mutation is what we look at in the tumor tissue to see if there are specific changes that will allow us to give a pill therapy, a targeted pill therapy. And then, there are also aspects of the tumor that help us figure out whether or not the immune therapy might work, and most commonly, that’s something called PD-L1. That’s a protein that we look at on the surface of the tumor, and so again, under the microscope.

Katherine:                  

And, when you talk about extracting DNA, is that via a blood test?

Dr. Wakelee:              

So, we have two different ways to do that. So, what I was talking about before was from the tumor tissue, you can extract the DNA. But now, there are these liquid biopsies where we can draw blood and find the tumor DNA that is different from the rest of the person’s DNA and look for those gene mutations in the tumor.

And that is where there’s a lot of developments happening. And, that’s so fabulous because they’re often faster results for patients, and it means that you can not have to go through another biopsy. We still need the biopsy to establish whether or not there is even cancer. But, once we know that there’s cancer for sure, then we can use the liquid biopsies to get a faster information result on those gene mutations and to follow over time to see how the tumor evolves because tumors change after they’ve been treated.

Katherine:                  

Do you use imaging at all?

Dr. Wakelee:              

Yes. Always. So, when someone is first diagnosed with cancer, we usually find that because of imaging, so, a CT scan or an X-ray, maybe they had a screening CT scan or maybe they had a cough that led someone to go get an X-ray, an examination. So, the imaging is a part of the original diagnosis. And in addition to CT scans, we’ll often get a PET scan that helps us look for, in a different way, the rest of the body, maybe an MRI of the brain to look in that area.

And then, wherever we’ve found the tumor, we will track that area with scans over time. And, it gets a little complicated for a patient that was found with what we call early-stage disease. So, stage I or II. Many of the times, those patients can have surgery and then we don’t have any tumor we can follow anymore. But we get CT scans to look to see if it could have come back. For patients with more advanced disease, so, stage III that couldn’t have surgery or stage IV, there we have areas that we’re going to continue to follow with the scans. And which scans and how often is going to depend a lot on what treatment the patient’s on and where the tumors are located that we’re tracking.

Katherine:                  

Do these tests differ for small cell lung cancer and non-small cell lung cancer patients? And, I know that non-small cell lung cancer is also known as NSCLC.

Dr. Wakelee:              

Yes. So, long ago, the only distinction we had with lung cancer was that small cell versus non-small cell, and that is something that is seen under the microscope when that tissue is taken out from the biopsy. The pathology doctors look at it under the microscope, and the cells look different. And, the small cell lung cancer, those cells are small. It’s not very creative naming. And then, everything else is non-small cell or NSCLC. So, it’s SCLC and NSCLC. So, that was one of the first distinctions.

And, it is still very important because the chemotherapy drugs that we use are slightly different. And, the genetic, those gene mutations, we see them in any cancer. That’s what makes a cancer different from the rest of the body. But in small cell lung cancer, the tumor mutations that we see are not things that we know how to target specifically. In non-small cell, there are targets that we can target specifically for some patients.

So, just there, it’s different in having the targeted pill drugs in non-small cell, not so much in small cell. With immune therapy, those newer immune therapy IV drugs, they can work in both small cell and non-small cell. But for small cell, the biomarkers, that PD-L1 level is not as important for helping us figure out who’s going to benefit. For non-small cell, with many of the drugs, it is important. So, there are differences there.

Katherine:                  

Well, let’s go a little deeper. And, you did mention some of this already, Dr. Wakelee, but what is genomic or biomarker testing?

Dr. Wakelee:              

So, we are struggling with how to have one unifying way of describing it because it’s so complicated. So, to me, biomarker testing is any aspect of the tumor that helps us choose the best treatment for that patient. And so, it’s a very broad term. And, within biomarker testing, there are several different ways that we look at it.

So, one is to look at what proteins are on the cell’s surface. And, we do that by having stains that we use to stain the tissue. So again, complicated, but when a piece of tissue is taken out of the person, part of the tumor is removed. It’s sliced into little tiny slices, which are then put on glass slides that can be looked at under the microscope. And, that’s how the pathology doctors can look and see, “Ah, this looks like cancer,” or, “It doesn’t look like cancer.” When it does look like cancer, you can then put on stains, so basically, different colored antibodies that will light up if that particular protein is there. And so, that helps us figure out for sure that this started in the lung because there are specific proteins that are only found in lung. So, that’s one way we used it, and this is an older technology. But, we also can use that to look for how much of this PD-L1 protein is expressed. And so, that’s an important biomarker, but it’s not based on genomics, which is when we’re talking about the DNA.

 Then, we have the genomic testing, and that’s when we’re looking at the genome of the tumor and how that genome is different. And, that’s that DNA or RNA testing. We talk about it with the next-gen sequencing. So, “sequencing,” any of those terms are all meaning we’re looking at some aspect of what makes the tumor genes and therefore the proteins made by the tumor different than the rest of the genes in the person.

And so, that testing, that genomic testing can be done on either the tumor specimen or that’s where we can do blood tests that will be able to pull out those bits of the DNA that are from the tumor versus from the person and help us figure out what’s going on with the cancer. So, when we talk about biomarkers, the whole picture, and when I’m talking with patients who are diagnosed with lung cancer, we talk about well, there’s chemotherapy treatment, which is good for almost everybody. There is targeted therapy.

Targeted therapy is usually based on those genomic tests, and the genomic tests can be done either on the tissue or on blood. But, they’re really important to have a full understanding of the tumors to do a comprehensive or next-gen sequencing analysis of the tumor or DNA. And then, you have the immune therapy where that PD-L1 biomarker is important. So, that’s the way I think about it, and the biomarkers are really critical for helping us figure out what’s the best path forward for any individual patient.

Katherine:                  

Let’s turn to treatment, Dr. Wakelee. On a basic level, what are the goals of treatment for lung cancer?

Dr. Wakelee:              

So, with lung cancer, we’d love to cure everybody, that’s the ultimate goal, and do it in a way where people are able to continue living their life as they were before the cancer diagnosis. The ways that we do it, first of all, we’ve got to find the cancer, and that’s where screening is such an important aspect of things. If we can find the cancer at an earlier stage, we’re more likely to be able to cure someone.

So, what do I mean by “earlier stage?” Well, when a tumor first develops, usually, there is a single cell that develops a mutation, meaning a change in the gene, which gives that cell an advantage so it doesn’t die the way it’s supposed to. And then, it keeps growing, and dividing, and making new cells. And those over time get to a large enough size that they are the cancer. And given more time, those cancer cells start to spread into other parts of the body, usually first into what we call the lymph nodes, and from there then into other organs in the body. And this stage refers to health or how the cancer spread. So, the stage I cancer is still in that ball of cancer. Stage II means that it’s spread into some lymph nodes. Stage III is it spread into more lymph nodes, usually in the center part of the chest or mediastinum, and that’s where it starts to be much more difficult for the surgeons to be able to truly remove all of the cancer.

And then stage IV means that the cancer is not something that we’re going to be able to remove with surgery. It’s spread either within the lung to the lining of the lung or it has spread to other organs in the body. And so, when we talk about those stages that I, II, III, IV, it’s a bit more complicated than that. But, I think for most people, if they just think about it as stage I, just the cancer, stage II, lymph nodes and the lungs, stage III, lymph nodes in the center, and then stage IV, elsewhere, that’s a good way to kind of wrap your head around it.

And when we talk about stage I and II, that’s the truly early stage where we hope to be able to cure people with surgery. Surgery alone is enough for the majority of people with stage I cancer, and for maybe half, a little more than half of people with stage II. So, how can we be better than that? Well, that’s where there’s been a lot of new advances. So, adding chemotherapy after surgery can help a lot of stage II patients.

If the tumor genomic testing biomarkers shows that there’s a mutation called EGFR, we now know that there’s a pill drug that people can take that would prolong the time to when the cancer might come back. And then, just very recently, there was stated that that immune therapy drugs IV can also prolong time to when the cancer comes back and maybe improve cure if the tumor has that biomarker called PD-L1. So, that’s that early stage. So it’s, again, getting more and more complicated and emphasizing that you’ve got to understand the biomarkers of the tumor to know how to best help someone.

When we move to stage III, some have surgery, but when you can’t have surgery, then we do the chemotherapy and the radiation. That’s the key part of the treatment there. And, we also know that immune therapy can be really helpful for a lot of patients when it’s given after the chemo and radiation’s completed. And then for stage IV, I talked about that already, which is you’ve got to do the biomarkers to figure out the best treatments for some people starting with a targeted pill drug is the right thing if their tumor has those right gene mutations.

For other people, immune therapy alone might be an option if the PD-L1 level is very high and they don’t have one of those gene mutations in the tumor. And for a lot of people, chemotherapy or chemotherapy plus immunotherapy is the right strategy.

Katherine:                  

Would you help the audience understand the types of therapy for small cell lung cancer specifically?

Dr. Wakelee:              

Yes. So, small cell still has the same kind of staging, but it’s a little bit more simple. We talk about extensive stage or limited stage. And what that has to do with is we rarely do surgery for small cell. It tends to have spread earlier. There are a few cases where that’s done, but normally, we divide it up into limited or extensive. And when we talk about that, limited is the radiation doctors can get all of the cancer in one radiation field, and then radiation plus chemotherapy is the standard approach to try to cure. If it’s more extensive than that, then it becomes extensive stage.

And, the best treatment are going to be chemotherapy plus those immune therapy drugs added together.

And so, the chemotherapy drugs that we use for non-small cell and small cell, the platinum drugs play a role in all of it. The drug we partner is a little bit different. There’s a drug etoposide we use a lot in small cell and a lot of other options for non-small cell. And then, the immune therapy drugs, there are a lot of options that are fairly similar for both small cell and for non-small cell. 

Katherine:                  

Dr. Wakelee, you mentioned targeted therapies. How do they work?

Dr. Wakelee:               

Targeted therapies are something we can use when we find a specific gene mutation in the tumor. So, I mentioned before that in order for a cancer cell to become cancer, something has to happen to the DNA in the cell.

And, there’s a change or a mutation in the DNA of the cell which leads it to be a cancer. And, a lot of the time, that mutation happens in a specific kind of gene that makes a type of protein called a tyrosine kinase. And for those of you who haven’t studied a lot of science, it’s a word you might not have heard before. But basically, these tyrosine kinases are proteins in the body that make a lot of changes to what’s going on in the rest of the cell. So, they’re sort of what we call regulators. And, one way of thinking about them is like on and off switches. So, normally, their job is to sit and if the right molecule comes around, that turns it on, and then it turns on other proteins in the cell. And if that molecule isn’t there, it’s turned off. So, it’s this on and off switch that does a lot of other aspects of what’s going on in the cell. But, sometimes, a mutation happens. It turns it on all the time. So, it’s like if you leave the light on.

It’s on all the time, that’s using a lot of energy, and that’s actually what’s driving the cell to act like a cancer. And so, we can now look for some of those mutations that turn some of these tyrosine kinases on all the time. But, we’ve also developed drugs that we can use to turn them off. So, if we find this specific gene mutation that’s turning, say, the EGFR protein on all the time, if we find that, we can have the patient take a pill that then turns that off.

And that helps the cancer slow down, some of it die, some of the cancer cells die, but it doesn’t completely wipe it out. It helps the patient for a long time though by shrinking the cancer, helping them feel better because the symptoms are gone, keeping the cancer from growing. But, cancer cells are clever. They continue to divide, they can continue to make new mutations, and eventually, they figure out ways around that. So, when we talk about targeted therapy, it’s a setting where we find the cancer.

In the cancer, we find the gene mutation, it’s in one of these specific types of proteins, genes that make specific protein that turn something on that we can then turn off, and with those pill drugs, we can have a big impact for people.

Katherine:                  

And, what exactly is immunotherapy?

Dr. Wakelee:              

Immunotherapies are treatments that were used to help keep the immune system more active.

So, the immune system is a very complex mechanism. There are cells that their whole job is to figure out and find things that are not us. So, they are looking for bacteria, they’re looking for cells that have a virus in them, and when they find it, they attack. And, that attack can be in the form of antibodies, it can be cells that actually go in and attack other cells directly, and we are all familiar a little bit with the immune system because we know that if we get a cold, our body, we can get a fever, that’s part of our immune response, and we get better. And then, some people know the bad side of the immune system if they have allergies or certain autoimmune diseases where the immune system gets a little bit too revved up and starts to recognize normal things as foreign.

So, in the setting of cancer, normally, the immune system is able to recognize a cancer cell, see that it’s different from the rest, and get rid of it. But, cancer cells are clever and they figure out ways to evade the immune system. And, one of the ways they do this is they put a protein called PD-L1. So, PD-L1 is a protein that a lot of our normal cells use to say, “Just a normal cell. Ignore me.” And so, when an immune cell comes in and sees that, it gets turned off it goes away. So, what our immune therapies do is most of them are blocking that PD-L1 protein. And, when they do that, it’s sort of like taking away the stop sign. So, you’ve got a tumor using a stop sign to say, “Go away, immune cell,” you block it so the immune cells can’t see that stop sign, and so then it kills the cancer cell better. So, that’s how these drugs work, and that’s the immune therapy.

There are some other stop signs besides PD-1 and PD-L1, but that’s the most common. So, when we’re talking about immune therapy, it’s drugs that block that. So, they increase the ability for the immune cell to recognize cancers. The risk from them is that you can get the body to recognize normal tissue as a problem sometimes. So, that’s the toxicity that we watch for.

Katherine:                  

Right. What are the advantages of these new treatment approaches compared to standard chemotherapy?

Dr. Wakelee:              

Well, I think the most exciting news that we’ve seen in lung cancer over the last few years is that we’re actually helping more people live longer. And the way that we’re doing that is through these newer treatments. So, when we can personalize treatment by recognizing that a person’s cancer has a specific gene mutation and we can give them the right targeted pill drug, we can help them live longer and feel better because those often have fewer side effects. Wish I could say they were curing the disease, but they’re helping people live longer.

And, that can be measured in years for some folks, which is fantastic. And then, with immune therapy, again, they’re not working for everybody, but they were for a large number of patients with lung cancer with non-small cell to help them live longer with their cancer controlled. And so, we’ve actually improved the overall survival rates for lung cancer with these new developments. Where we can make even more of an impact is also by finding more of the cancers earlier, and that’s where cancer screening is so important also. So, by having more choices, chemotherapy can still help a lot of people. Targeted therapies can help probably close to 20, 30, 40 percent of people with non-small cell lung cancer that’s the adenocarcinoma type. And then, the immune therapies can help other people living with lung cancer. Usually immune therapies don’t work on the same tumors the way the targeted pills work. So, you’re kind of getting at different groups of people with those different strategies. It’s not completely true, but it’s a kind of general principle about it.

Katherine:                  

What about side effects for some of these treatment choices?

Dr. Wakelee:               

So, chemotherapy is one people fear the most, but I think it has a bit more of a bad reputation than it needs. A lot of the lung cancer therapies that are chemotherapy can be reasonably tolerated. I mean, I’m not signing up to go get chemotherapy just because. There definitely are side effects. The biggest one is people get fatigue, get really tired. Though, if they’re feeling horrible because of the cancer, a lot of times people feel dramatically better. But, tiredness, it can impact appetite a little bit, though cancer does that also. There can be nausea, vomiting, but we’re much better at controlling that with the newer drugs. Some cancer therapies cause hair loss, but a lot of our non-small cell lung cancer therapies don’t cause hair loss. So, there are a lot of options there you can talk about with your doctor. And then, when the blood counts are low, there can be risk for infection, low red blood cells with anemia.

So, there are a lot of different things. But in general, chemotherapy is better tolerated than people think it’s going to be because in the movies, they make it look horrendous.

With the pill therapies, again, lots of variability depending on the specific pill. Some of them cause rash. Some don’t. Some of them can cause some changes to the heart that we have to monitor with EKGs, electrocardiograms, some don’t. Some cause some changes to labs like for liver tests that we have to monitor. Some don’t. Some cause hair color changes. Some don’t. It’s always to gray, unfortunately.

So, there are a lot of different variations in what different treatments can do. And so, it’s just really important if your doctor is talking with you about starting one of the targeted pill drugs that you really ask what are the side effects I need to be watching for, what are the ones I need to know to call you about, and which are the ones I just know, “Okay, this is happening and it’s okay. It’s going to cause swelling in the ankles,” no, just a huge range of them. And then, with the immune therapy drugs, they tend to be mostly fatigue, just like with chemotherapy, though some people feel fine.

What we have to watch for is that they can cause what we call autoimmunity. So, it’s talking about the fact that the way they work is they help the immune system better recognize the cancer, and they do that by taking away one of the stop signals. But, that stop signal, the PD-1, PD-L1, that stop signal is also used by a lot of normal cells to tell the immune system to back off. So, when you remove it, when you block it, the immune system can get confused and start to attack normal cells. So, you can get a rash, people can end up with gut symptoms like diarrhea, they also can end up with it attacking the lungs and causing what we call a pneumonitis lung inflammation or brain symptoms, so, almost anything. Now, those are rare, and we can treat them with steroids. But, people need to be aware that if something new is happening, they need to alert their doctor. I think sometimes, there’s this false impression that immune therapy is completely safe, but, it’s not. And, all of the treatments that I’m talking about are designed to help people live better and live longer when they’re dealing with lung cancer, but they all also have risk.

And so, it’s just really important to have those discussions with the care team as you’re starting something new about what are the things I need to be watching for and to know how to reach people if you’ve got a new and concerning symptom, especially if you’re starting on something new.

Katherine:                  

That’s all really helpful information. Thank you, Dr. Wakelee. We have a question that we received from an audience member earlier. Jeff asks, “How do you know if your lung cancer treatment is working?”

Dr. Wakelee:              

So, there are a lot of ways of knowing if treatment is helping. So, the one I rely on the most is, “Does the patient overall feel better?” That is difficult to say exactly how. Sometimes people are having breathing problems; they feel that that’s better. Sometimes their energy’s lower. They feel better. It can be vague. We also use scans. So, we tend to get scans, depending on the treatment we’re giving, every couple of months plus or minus, sometimes, every three months to help track what’s actually going on. But occasionally, there are discrepancies.

So, sometimes, the scan, is it better? Is it not better? Can’t really tell. And then, you’re always taking that, “How does the patient feel?” So, usually, if the scans are better, the patient feels better. It’s easy. Usually if the patient’s feeling worse and the scan looks worse, clear decision. Not a good one, but clearly, we need to do something different. But sometimes, you’re left, and especially this happens with the first scan because you get a scan, it takes a little while, you start the new treatment, then you get the next scan, how much of the changes happened before you started the new one and how much didn’t? So, these can be more challenging conversations, but generally if the patient’s feeling a little bit better, the scan’s unclear, we usually say, “You know, let’s give this treatment a little bit more time.” We also, I think your question was specifically around how do we tell if it’s working, but, you also often need to be thinking about, “Well, what’s it doing that’s negative to the person and is that potential, those side effects worth the benefits we are or are not seeing?”

So, it’s kind of all of those things together. It can be a bit complex.

Katherine:                  

What goes into the decision to change therapies if it becomes necessary?

Dr. Wakelee:              

So, when we’re thinking about making a change, the way I always look at it is, is where we are today still okay or not? And, if it’s not, that would be because clearly the cancer’s growing or clearly the side effects are just not tolerable. Then, we decide together with the patient we need to do something different. And, when we think about what do we do next, we look at what have we’ve already done, did it work or not, if not, let’s do something more different. And so, let’s think about something that might be somewhat similar. When we’re dealing with targeted therapies, we have ways to try to figure out what changed in the tumor that made it now resistant or not working with that treatment. And so, with some of the pill drugs, there’s been a lot of research and understanding how does the tumor change that helps it evade, get away from, be resistant to whatever treatment you’re on.

And then, sometimes, we have other pill drugs that work in that particular setting, not always. With immune therapy, we’re trying to better understand why does the immune therapy stop working? Sometimes you can add back to it, like, you can add chemotherapy back to immune therapy alone or sometimes you can do radiation with immune therapy to get that response back. Or, add other combinations to it. So, that’s another thing that we’re working on. And then, like I said, if someone hasn’t ever had chemotherapy and the tumor’s become resistant, we’re going to be thinking a lot about chemo because that can play a role against so many different reasons that the cancer might not be responding to whatever treatments someone’s on. And then also, looking at how the patient’s feeling and doing, what their overall what we call “performance status, ” their sort of overall health, and how well do we feel with them that they’re going to be able to tolerate the next treatment because, you’re always having to weigh how much is this likely to help, and how might this harm in finding the right balance.

Katherine:                  

I’d be remiss if I did not bring up COVID-19, and, I’m sure a lot of patients are curious whether the vaccine is safe and effective.

Dr. Wakelee:              

So, we do believe the vaccine is safe and effective for patients living with lung cancer, and really important to be protected as much as possible. I was part of a group of other physicians around the world looking at the impact of COVID-19 on patients living with lung cancer. And, we collaborated with a group of physicians, Rayna Garcina was the lead. She was living in northern Italy at the time of the first wave, and so, was really face-to-face with it early on when there was so much we didn’t know. And, she gathered a group of us to watch and see, and what we were able to figure out before the vaccine was available was that people living with lung cancer who were overall healthy still except for their cancer were perhaps on a pill, targeted therapy, or immune therapy seemed to really not have that different of an impact compared to people who didn’t have lung cancer.

Chemotherapy was a little bit harder to see that, but didn’t seem to be such a big issue. It’s different than people living with, say, leukemias or lymphomas where the treatments are impacting their immune systems even more. They seem to have worse outcomes. A lot of lung cancer patients were okay, but still, it’s a higher risk. And so, we want to protect our patients as much as possible.

So, we are, now that we have the vaccines, strongly advocating vaccines for any patient who was living with cancer really for almost anybody because as a physician, we really think that makes a big impact. We have not seen any negative impacts of the vaccine on any aspect of cancer treatment. It does not have a negative impact on how well the cancer is treated by the therapies. We did notice that when someone gets the vaccine, they can get some enlargement of the lymph nodes. That’s part of having an immune response is your lymph nodes get enlarged. And so, we did get a bunch of scans that the vaccines came out showing, “Well, this person has some lymph nodes in the axilla, which is the armpit.”

And it seemed to be correlating with the side that someone had a vaccine. And then, those go away. And, this was actually an interesting medical literature thing because for people getting screened with mammograms for breast cancer, there were suddenly all these lymph nodes showing up. But that was actually a sign that the person was responding to the vaccine and it went away over time. And, it was a fine thing. It was just – I remember the first patient I had where that happened, we’re like, “Oh, well, that makes sense. Okay.” So, it’s okay. So, it was not cancer. It was just the immune response. But, yeah, so, we are recommending vaccines. There’s no data showing it is not working for lung cancer patients. The vaccines are less effective in people getting certain types of cancer treatment that are really suppressing the immune system. But even some response is better than none, and we’re still recommending the patients really do their best to stay safe with masks and things like that.

Katherine:                  

Dr. Wakelee, what are you excited about in lung cancer research right now? And, what do you want to leave the audience with? Are you hopeful?

Dr. Wakelee:              

I’m very hopeful. When I started treating lung cancer patients 20 years ago, we only had chemotherapy. And now, for metastatic disease, with using the right biomarkers, we can figure out so much more about the cancer to be able to personalize the treatment, for many patients, being able to offer pill therapies that are somewhat less toxic and highly active and give people more time. And now, we’re in the immune therapy revolution, which is helping a whole other group of patients living with lung cancer to be able to live with quality life for much longer. And the pace of discovery is just going up so quickly. And, I think that’s what I’m most hopeful about is just how much attention is being paid on lung cancer and finding better therapies that are going to help more people for a longer period of time. And again, I’m going to emphasize the screening is making a big difference also. If we can find the disease early, we can have an even bigger impact on people.

Katherine:                  

Dr. Wakelee, thank you so much for joining us today.

Dr. Wakelee:              

Thank you. Really enjoyed talking with you. Thank you.

Katherine:                   

And thank you to all of our partners.

To learn more about lung cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.

Why Should You Ask Your Doctor About Prostate Cancer Genetic Testing?

Why Should You Ask Your Doctor About Prostate Cancer Genetic Testing? from Patient Empowerment Network on Vimeo.

Why is it genetic testing important when it comes to prostate cancer care? Learn how test results could reveal more about YOUR prostate cancer and may indicate that one treatment may be more effective than another.

See More From INSIST! Prostate Cancer

Related Resources

How Does Genetic Testing Impact Prostate Cancer Care?

Treatment Options for Advanced Prostate Cancer

What Is a Prostate Cancer Genetic Mutation?


Transcript:

Why should you ask your doctor about genetic testing?

The test results may predict how your prostate cancer will behave and could indicate that one type of treatment may be more effective than another type.

Genetic testing identifies specific gene mutations, proteins, chromosomal abnormalities, and/or other molecular changes that are unique to YOU and YOUR prostate cancer.

There are two main types of genetic tests used in prostate cancer:

  • Germline or hereditary genetic testing, which is conducted via blood or saliva and identifies inherited gene mutations in the body. Germline mutations are present from birth and can be shared among family members and passed on to subsequent generations. Results can identify whether you could be at risk for another type of cancer or if your family members may need genetic counseling and testing to guide their own cancer risk.
  • The second is somatic or tumor genetic testing, which is performed through testing tumor tissue or by testing cancer cells/DNA extracted from blood to identify gene mutations that are unique to the cancer itself. It is also commonly referred to as genomic testing, biomarker testing, or molecular profiling. Somatic mutations are NOT inherited and are NOT passed on to subsequent generations or shared among family members.
  • Depending on your history, your doctor may order one–or both–of these types of tests.

So why do the test results matter?

Both germline and somatic mutation testing can identify the presence of certain genetic mutations that may help to guide your treatment plan, and germline testing specifically can inform cancer risk for you and, potentially, family members.

  • In some cases, mutations can indicate that a newer approach, such as targeted therapy or immunotherapy, may work better for you.
  • Results of these tests may also help you to find a clinical trial that may be appropriate for your particular cancer.
  • And, genetic testing results could also show that your cancer has a mutation or marker that may prevent a certain therapy from being effective, sparing you from getting a treatment that won’t work well for you.

How can make sure you have had essential biomarker testing?

  • First, always speak up and ask questions. Remember, you have a voice in YOUR prostate cancer care.
  • Ask your doctor if you have had or will receive genetic testing, including germline and somatic testing, and how the results may impact your care and treatment plan.
  • Ask whether your family members should meet with a genetic counselor or undergo testing to help gauge their risk of developing prostate cancer.
  • And, finally, bring a friend or a loved one to your appointments to help you process and recall information.

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

Which Metastatic Breast Cancer Treatment Is Right for You? What You Need to Know

Which Metastatic Breast Cancer Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What do you need to know before deciding which treatment is best for YOUR metastatic breast cancer? Expert Dr. Jane Meisel reviews recent research news, discusses the role of key tests–including biomarker testing –in determining a treatment plan, and shares advice for self-advocacy.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel, here.

[Editor’s Note: On August 23, 2021, the U.S. Food and Drug Administration (FDA) approved the Pfizer-BioNTech COVID-19 Vaccine for individuals 16 years of age and older.]

Download Program Guide

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

What Could Advances in Breast Cancer Research Mean for You?

How Can You Advocate for the Best Breast Cancer Care?

Factors That Guide a Metastatic Breast Cancer Treatment Decision

 


Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. In today’s webinar, we’ll discuss how you can access the most personalized metastatic breast cancer therapy for your individual disease and why it’s vital to insist on key testing. Before we meet our guest, let’s review a few more 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 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 plan future webinars. And finally, before we get into the discussion, please remember, this program is not a substitute for seeking medical advice. Please refer to your healthcare team – Please refer to your healthcare team about what might be best for you.

All right, let’s meet our guest today. Joining us is Dr. Jane Meisel. Dr. Meisel, welcome. Would you please introduce yourself?

Dr. Meisel:

Absolutely and thank you so much for having me. My name is Jane Meisel and I’m a medical oncologist at the Winship Cancer Institute at Emory University. I’ve been here for about six years and before that, I did my training in Boston and at Memorial Sloan-Kettering in New York. And I specialize in breast cancer and have had a lot of great opportunities to treat amazing patients and participate in a lot of research.

And I’m looking forward to having this discussion with you today.

Katherine:

Thank you for joining us, we really appreciate it. So, let’s start by discussing the latest developments in treatment and research updates. Are there recent developments you feel breast cancer patients should know about?

Dr. Meisel:

Absolutely and I think it’s really been such a remarkable time because even during COVID, a pandemic, where I think a lot of people worried that research efforts would shut down or stall. We’ve still seen the approval of a number of drugs in the past year that’ve really already markedly changed lives. And a lot of important findings that’ve come out of other trials that they have opportunity to do that as well.

I think some of the biggest information that was presented at our most recent large meeting, which was the American Society of Clinical Oncology, or ASCO National Meeting in 2021, were a few things that pertain to the metastatic breast cancer population. One was two studies, the PALOMA-3 Trial and the MONALEESA-3 Trial, which looked at a class of drugs called CDK4-6 inhibitors along with anti-estrogen pills in metastatic estrogen-positive breast cancer.

And really confirm for patients that not only do these drugs improve the amount of time that people can stay on treatment before their cancer progresses, but actually improve how long people live. Even when they’re used very, very early on in treatment, they impact survival down the line for many, many years. So, it really confirms for physicians like me that this class of drugs should be used as the standard of care and first line for patients with estrogen-positive stage IV breast cancer, and I think that’s important for patients to know. Along those lines, there a drug called sacituzumab govitecan, or Trodelvy, which is a much easier to say name.

Katherine:

Yes.

Dr. Meisel:

A new antibody drug conjugate in triple-negative metastatic breast cancer. And we’ve also seen, since this drug was approved last year, it has markedly changed the lives of many patients with triple-negative disease. And the study called the ascent trial, which is what led to that drug’s approval was studied further and some of these additional results presented at ASCO this year.

And found that this drug not only improves again, how long people get before they have to move on to another treatment, but actually improves how long people live as well, even when given later on in the course of therapy. So again, really encouraging use especially in triple-negative metastatic disease, which is hard to treat. And I think another study that’s really worth patients and doctors taking a hard look at, was actually a study that looked at patient outcomes and patient experience. This is a study that actually talked with metastatic patients and gathered their views on treatment related adverse effects.

Talked to patients about what adverse effects they were experiencing from drugs. How they managed those adverse effects. And found that most patients, over 90%, will be willing to talk about reducing the dose of drugs or changing dosing schedules, in order to improve quality of life. And I think that’s really important because a lot of times, the doses of drugs that get approved are the doses that are the highest doses that don’t cause extreme toxicity. But sometimes people can have effective, really good outcomes on lower doses and have much better quality of life.

And in metastatic breast cancer where really the goal often times is to help people live as long as they can, but also as importantly, as well as they can, be able to have those open-ended conversations between patients and doctors about what’s really impacting your quality of life now and how can we make that better is important. And this study I think really highlighted that both for patients and physicians, how important that back and forth is to having a successful outcome. Both in terms of how life is lived, but in terms of quality of that life.

Katherine:

Right. Right. How can patients stay up to date on developing research?

Dr. Meisel:

It’s so interesting because there is so much coming out and I think it can be hard to figure out what Phase I study that looks exciting is really going to become something, versus what really could be important in my treatment today. And what I always tell people is actually, the NCI website. So, the National Cancer Institute, has a phenomenal page looking at advances in breast cancer research. So, if you Google “NCI advances in breast cancer research,” there’s a great page that comes up. And it’s impressively up to date and I think very patient-friendly.

Breaks things down into early stage and metastatic and then in the metastatic section, talks about estrogen-positive, HER2-positive, triple-negative, which we can talk about more today but are the three big subtype of metastatic disease that dictate how we treat them. And then have links to all the different research updates and talk about what these drugs are, what the classes are and what the settings are in which they’re studied.

And so, I think that’s a really great first stop and then the links can take you to all different stuff that’s on the page that you might want to look into more in depth. And then also, the Breast Cancer Research Foundation, which is a phenomenal organization. They have a great website, too and if you click around on the website, you can see not only who they’ve donated money to that’s doing promising research, they also have podcasts, they have a blog with science and research news. I think that’s a really great site for patients to use to stay updated.

Katherine:

Let’s shift gears for a moment and talk about another time sensitive topic, COVID. Now that vaccines are available, are they safe and effective for breast cancer patients?

Dr. Meisel:

Yeah, I think the short answer to that is yes, absolutely. I’m encouraging all my patients, no matter what their treatment status is to go ahead and get vaccinated. And we are seeing now this third surge in COVID with cases rising all over the country, and really among unvaccinated populations. And with the delta variant being more transmissible, I think it’s all the more time, even if you haven’t considered vaccination up until now, to really go ahead and strongly consider getting a vaccine.

I think some of the hesitations that some of the people have talked to me about is that there were not a lot of active cancer patients, if any, included in the initial trials. And whereas that is true, it’s still the case that now, so many cancer patients have been vaccinated. We haven’t really heard about adverse effects in vaccination being something that’s higher in patients who have cancer who are on active treatment. I think the one challenge is, if you have a compromised immune system because of cancer treatment, there’s the possibility that you might not mount the same immune response to the vaccine as someone who doesn’t have cancer or isn’t getting active treatment.

So, while I would say yes, definitely get vaccinated, I would also at the same time encourage caution in saying, because you might not mount the same, 95 percent or whatever immune response, it may still be a good idea to wear a mask when you go to the grocery store, taking those precautions because no one really knows what’s coming and it’s better to be safe than sorry. But I think we will get a lot of information as the months go on about, do we need boosters? Who might need boosters more soon than others and some of that will get clarified for us, but my short answer would be yes, vaccines for all.

Katherine:

Excellent, that’s very helpful.

Dr. Meisel:

Thank you.

Katherine:

Since this webinar is focused on metastatic disease, would you define metastatic breast cancer for us?

Dr. Meisel:

Absolutely. And I think metastatic breast cancer is one of those terms that as doctors, we throw around a lot and often times don’t stop to check understanding as to what that means.

And what metastatic breast cancer is and means, is breast cancer that is spread outside of the breast and surrounding lymph nodes to another organ system. So, metastatic breast cancer, some of the most common places where it spreads are to the bone, to the skin, to the lungs, to the liver, to the brain. There are other places it can spread to. I’ve seen it on the ovaries, in the GI tract. But basically, when breast cancer spreads outside of the breast and surrounding lymph nodes to another organ system, that’s when we consider it metastatic.

Katherine:

How can a patient ensure they are getting an accurate diagnosis?

Dr. Meisel:

Another good question. And I think the most important thing when you’re considering whether or not you have a diagnosis of metastatic breast cancer is to get a biopsy of that metastatic site. So, you wouldn’t want to assume, just based on a CT scan that shows something in the bone that you have metastatic disease. Ideally, we would biopsy that spot or some spot that was indicative of metastatic disease to actually prove that there is metastatic cancer in that distant site.

Because sometimes it’s nothing. Sometimes you get scans and a little bone abnormality, maybe a scar from a prior fall. And then also, sometimes if it is metastatic, sometimes the breast cancer, the hormone receptor status, for example, can change from the primary site to the metastatic site. And that might impact treatment. So, it’s important to both get a metastatic biopsy to confirm diagnosis. And also, to understand what the treatment plan might be. And I think also for patients, just to make sure that you understand what your stage is, ask your doctor.

Say, what is my stage? Because sometimes doctors think people understand and they don’t actually, so checking that understanding is important. But if your doctor or provider is not actively checking your understanding, you can check it with them to make sure that if you are metastatic or have Stage IV disease, which is another way we define metastatic or talk about metastatic cancer, that you make sure you have the definition right.

Katherine:

Right, right. So, once someone has been diagnosed with metastatic disease, are there key tests that’re used to help understand how their disease may behave and progress?

Dr. Meisel:

Absolutely. So, I think the first thing as I said is that metastatic biopsy. Another thing that’s very important is understanding the hormone receptor status and the HER2 status of the breast cancer. And probably for a lot of you listening, if you have listened to metastatic breast cancer webinars before or maybe know someone or have had a diagnosis yourself, you’re well versed in this. But for some who may not be, I think a quick overview is maybe helpful. Breast cancer can be divided into three different subtypes. So, triple-negative, estrogen-positive or HER2-positive. And estrogen-positive breast cancer is the most common kind.

That tends to be driven by hormones and often treated with what we call, endocrine therapy. So, anti-estrogen pills, things like Tamoxifen or aromatase inhibitors are examples of that. And that’s one kind. And then there’s HER2-positive breast cancer, which is a type of breast cancer that over expresses a marker called HER2. And we now, since we know about that marker, have been able to develop a lot of different treatments that target HER2 selectively.

And can be used to treat that subtype. And then triple-negative is basically estrogen-negative, progesterone-negative and HER2-negative. And that type of breast cancer traditionally was treated essentially only with chemotherapy. But now we’ve had some breakthroughs, which we’ll talk about I think later in this program talking about immunotherapy and more targeted therapy for that. But those subtypes help determine how we treat patients. And it also can sometimes predict behavior.

I would say one of the other things that helps us predict behavior of metastatic disease is, if a patient had early-stage disease before, how quickly they developed metastatic disease. So, for example, someone who develops estrogen-positive metastatic breast cancer 12 years out from their original diagnosis is statistically more likely to have a slower progressing course of disease than someone who develops triple-negative metastatic disease very soon after their initial treatment. So, I would say that’s the primary thing we look at in terms of determining treatment plan and then predicting overall course.

Katherine:

Right. Well, let’s talk about treatment options for advanced disease.

Can you review the types of treatments available for metastatic breast cancer?

Dr. Meisel:

Absolutely. And what I’ll do is, I’ll give you a broad overview and then because there’s so much and this is such a rich environment, I mean, I give hour long lectures just about the treatment of metastatic triple-negative breast cancer to our fellows. So, there is so much meaty information here. But I’ll give an overview with some key buzzwords so then people can go look up things that matter more to them or interest them more. So, as I said, we start with thinking about, is this hormone receptor-positive or estrogen-positive breast cancer? Is this HER2-positive or is this triple-negative? And those factors really send us down different paths.

So, if someone is estrogen-positive, I had mentioned before the PALOMA and MONALEESA studies showing that CDK4-6 inhibitors, which is a class of drugs that the first one was approved in 2015 and then two others have been approved subsequently. So, relatively new drugs. But those drugs, which are pills, added to traditional anti-estrogen therapy which would be aromatase inhibitors or fulvestrant.

Are often great first-line options for these patients. And people can do well for years on just that alone, with estrogen-positive metastatic breast cancer. On average, about two years before people progress and need something new. And then after that, there are lots of trials ongoing looking at different ways in which an estrogen-positive breast cancer might progress on that regiment and how do we target that. So that there are multiple other anti-estrogen options down the line that people can use in estrogen-positive breast cancer before they need to even think about going on to something like chemotherapy.

So, really lots and lots of options for those patients, but probably starting with a CDK4-6 inhibitor plus anti-estrogen combination. And then in HER2-positive breast cancer, typically the first-line treatment would be what we call monoclonal antibodies directed at HER2. So, something like Herceptin and Perjeta, which you may have heard of. And often combined with chemotherapy. But again, this is one of those areas that is also very, I think the art of medicine is very important and patient dependent.

Some of these regiments depend a little bit on patient’s age and other medical problems and desires, whether to include chemotherapy along with that frontline anti-HER2 regimen. Or whether to think about something like anti-estrogen therapy if the patient is HER2-positive and estrogen-positive. And then there are a lot of other different things we’re also using in HER2-positive disease after patients progress on that initial therapy, so there are what we call, antibody drug conjugates, where a chemotherapy like drug is attached to an antibody that then brings the chemo to the HER2-positive cell and allows for chemotherapy penetration more directly.

And then a class of drugs called tyrosine kinase inhibitors, which are oral drugs that get directed at HER2. So, another really exciting area to treat and a place where we’ve seen so many advances. And then in triple-negative breast cancer, I’d mentioned that chemotherapy has really been the mainstay of treatment historically because there weren’t great targets. But recently we’ve seen that immunotherapy, along with chemotherapy drugs like Keytruda, which you may have heard of.

Or atezolizumab, which is Mesenteric, can be used along with chemo and patients that overexpress a molecule called, PDL1. And that can actually include not just how long patients spend on the first treatment, but how long they live. So, we’re seeing a lot of triple-negative patients being great candidates for immune-based regimen now. And then for patients who have inherited a BRCA gene mutation, which many of you may have heard of. That gene mutation can actually predispose a triple-negative patient to be more receptive to a class of drugs called PARP inhibitors.

So, drugs like olaparib (Lynparza) or talazoparib (Talzenna) are new drugs that’ve been approved in the last couple of years in triple-negative metastatic breast cancer for patients who carry a BRCA1 mutation or BRCA2 mutation. And then there are also antibody drug conjugates in triple-negative breast cancer as well. The Trodelvy that’s been approved and then of course others that are in clinical trials currently. So, as you can see, it’s complex. I mean, the treatment of metastatic breast cancer is complicated. And so, it’s important I think to really be able to have a dialogue with your provider about what they’re recommending for you and why.

And I think there are often lots of options. And so, as much as you can make your doctor aware of what matters to you in terms of what side effects are you most afraid of or would you like most to avoid, what dosing schedules would be idea for your schedule for the rest of your life. So that you can deal with taking kids to school or the job that you’re currently working on or whatever, I think helps your doctor help you come up with the right regiment for you.

Katherine:

Yeah. Yeah. So, what factors are considered when deciding on the best treatment approach for an individual patient?

Dr. Meisel:

So, I think certainly the tumor type that we were talking about. Is it estrogen-positive or HER2-negative or HER2-positive? I think response to past treatments, both in terms of if someone has had metastatic disease for a long time and has had a few treatments already, how long did they respond to those treatments and how completely did they respond to those treatments. Did they have stable disease for a while or did their cancer actively shrink?

And then I think other than that, it would be some of the things I touched on. Side effect profiles. Do patients have pre-existing neuropathy from other chemotherapy? If so, maybe you want to avoid a regiment that causes more neuropathy. Schedule. Some patients, it’s really important to be on a certain schedule, as opposed to a different schedule. I think whether there are clinical trials available instead of whatever the standard of care regiment would be is also important.

Because for some patients who are interested in pushing the envelope or who might be a great candidate for a particular trial, if there is one that they’re a candidate for that’s not horribly inconvenient from a logistics standpoint, then trials I think are also a great option to consider. So, I think from an effectiveness standpoint, you want to think about the tumor type response to past treatments. And then potentially, if the patient has had, what we call genomic profiling, where the tumor has been sent for basically genomic analysis, to see what genes might be mutated in the tumor that could potentially drive a response to a newer, different therapy.

All those things can be taken into account as we think about the cancer. But then there is the patient specific factors, and I think those would be mainly side effects, schedule, clinical trials and desire or not to pursue those. And then, just what the patient’s perspective is on the plan that you’re offering them.

Katherine:

What is biomarker testing and how do results impact treatment options?

Dr. Meisel:

Great question. So, I think people often confuse germline mutations and somatic mutations. So, I’ll talk about that a little bit as we talk ab out biomarkers. So, I think biomarkers in general are factors within the tumor that allow us to make treatment decisions. So, if a biomarker in the tumor can predict response to a certain type of treatment, we want to know what that biomarker is so we can better treat the patient and more elegantly design a regimen. So, for example, having an estrogen-positive tumor, estrogen positivity is a biomarker suggestive of response to anti-estrogen treatments, which is why we give anti-estrogen therapy to ER-positive breast cancers.

But more recently, we’ve been able to move a little bit beyond estrogen, HER2- and triple-negative as our subtypes and think a little bit more in some patients about more sophisticated biomarkers. And that’s where somatic mutation testing comes in. So, there are germline mutations, which are inherited mutations that’re present in every cell in your body. So, for example, if your mother was a BRCA mutation carrier and based that BRCA mutation down to you, you would have a germline BRCA mutation. So, your cancer would carry a BRCA mutation, but so would every other cell you have.

And that’s a biomarker. That would make you a candidate for something like a PARP inhibitor. But in cancers, which the genes in the cancer have gone awry by definition, there are often other biomarkers within that tumor that may make you a candidate for certain treatments. And so, those mutations that arise in the cancer itself are called, somatic mutations. Those are mutations in the tumor, can’t be passed down to your offspring or anything like that and were not inherited by your parents. But mutations that’ve accumulated over time as these cancer cells have gone awry.

And so, genomic testing, or biomarker testing can be done often on a metastatic specimen. So, to be specific about it, say you had a metastatic breast cancer to the liver. You could have a liver biopsy done and that tissue from the liver biopsy could be sent for genomic testing. There are a lot of companies that do this and there are also some larger cancer centers that actually do in house testing for genomics. So, this testing can be done and what it does then is, it helps you determine, do you have a biomarker that predisposes you to a certain treatment.

So, if that metastatic liver tissues, for example contained high levels of PBL1 expression for example and you were triple-negative, that would say to your doctor, “Ooh, this is a great candidate for immunotherapy along with chemotherapy.” Or if you’re estrogen-positive, for example, and your tumor contains a mutation in the gene called PIK3CA and that might make you a candidate for a drug called, alpelisib (Piqray). So, these mutations could often be paired to a drug or treatment options, or sometimes to a clinical trial to allow patients to come take advantage of more targeted therapies.

That sometimes, because they’re targeted, have fewer side effects than drugs that are a little more discriminate.

Katherine:

Marie sent in this question prior to the program. Are there some genetic tests that’re more accurate than others?

Dr. Meisel:

That’s a good question. I would say most genetic testing platforms have been heavily vetted and approved by national organizations and laboratories that’ve been tested multiple times before they’re allowed to be marketed. So, I wouldn’t say that one genetic testing program is necessarily better than another. I think that any of the commercially available platforms that’re used are probably pretty accurate.

Katherine:

Okay. How does symptom management play into the treatment decision?

Dr. Meisel:

I was just going to add one thing to that, if that’s okay. I was going to say that I think it’s important when you’re using genetic testing platforms though to know what you’re testing for. So, there are some platforms that will just test for say, the three most common mutations in BRCA1 and BRCA2 that Ashkenazi Jews have.

And so, if you get that testing back and you’re negative, you might think oh, I don’t have a mutation in those genes. Well, we know from that testing, just as an example, is that you don’t have a mutation in those three alleles of that gene. But if you haven’t had full gene sequencing, you could have a mutation somewhere else in that gene. So, I would say all genetic testing that’s commercially available is probably pretty accurate. But it is important when you get testing done to know what you’re testing for and what you’re not testing for so you can interpret your results accurately. And genetic counselors, as well as your doctors can help you do that.

Katherine:

Right, right. Okay, I’m going to ask the question, this question again. How does symptom management play into the treatment decision?

Dr. Meisel:

I think symptom management is huge, because like I said and I tell this to all my patients at the outset of treatment that most of the time, metastatic breast cancer becomes a chronic diagnosis for a patient. You’re dealing with it, essentially like a chronic illness for the rest of your life. And you’re on some form of treatment for the most part, for the foreseeable future.

And so, making sure quality of life is as good as it can be is critically important. And I think symptom management is a huge part of that and we know that if we can treat and manage symptoms well, people can live better and often live longer because then they can stay on treatment for more extensive periods of time comfortably. And so, I always encourage patients, don’t be a martyr.

Don’t think you have to just bounce in here and tell me everything’s okay if it’s not okay. If you’re having symptoms and side effects from treatment, or from the cancer, I want to know about them so that we can really aggressively manage those symptoms just like we’re aggressively managing the cancer. A lot of times oncologists can do that on their own. We are pretty well versed in managing a lot of symptoms and side effects.

But a lot of times also, there are teams of doctors either who do palliative care or here at Emory, we call it supportive oncology where they are specially trained in things like pain management and managing more common side effects like nausea, constipation, diarrhea, appetite suppression, that can go along with cancer and with treatment.

And then they often will co-manage patients with us as well, just to make sure there’s that really strong focus on maintaining as much of a low symptom burden as possible.

Katherine:

So, you mentioned earlier, clinical trials. When should patients consider participating in a trial?

Dr. Meisel:

I think it’s a great question and I think the answer is really, almost any time. There are trials in every setting. So, I think one of the common misconceptions about clinical trials is that you really only should be in a clinical trial, or your doctor might only mention a clinical trial if they don’t have other options for you or if you’re really in stage. And I think that perception is changing. But I think the reality is that there are clinical trials in every setting.

So, we have clinical trails looking at prevention of breast cancer. Clinical trials looking to optimize early-stage treatment of breast cancer. Clinical trials looking at secondary prevention, so once you’ve had breast cancer, how can we reduce your risk of recurrence. And then lots of clinical trials in the metastatic setting both for patients who are initially diagnosed with metastatic breast cancer.

And then in second, third, fourth line and even for patients who have had tons and tons of additional therapy that we’re looking at new drugs for. So, I think at almost any juncture where you’re making a treatment change, it’s probably appropriate to say, would there be a clinical trail that you can think of that would be good for me in this setting? And it may be that there’s a one that’s 12 hours away, and it’s not convenient for you or feasible.

And it may be that your doctor doesn’t necessarily know of one but then that prompts them to ask a colleague who may be more involved in clinical trial design and development. Or it may be that there is one, but you ultimately choose not to pursue it because you have a different option. But I think it’s always appropriate to ask, would there be a trail for me? Because if there is, then maybe that opens up an option you hadn’t thought about before.

Katherine:

Sure. For patients who aren’t familiar with the stages of clinical trials, would you give us a brief overview of the stages?

Dr. Meisel:

Yeah. Absolutely. So, in terms of clinical trials that’re being done in humans, we talk about Phase I, Phase II and Phase III typically. So, a Phase II clinical trial is typically an earlier stage trial.

Looking at either a drug that has not been tested in humans before or a drug that has not been tested in a particular combination in humans before. And so, those trials are done only in select institutions, usually academic institutions as opposed to private hospitals. And they often have what’s called a dose finding phase and then a dose escalation phase. So, the earliest part of those trials is actually looking at, what is the safest dose to give to patients?

So, they start the first patients at a low dose of the compound. And if those patients do well, the next patients that’re enrolled get enrolled at a slightly higher dose. And then up until they reach the highest dose they can find where people are tolerating it and doing reasonably well. And in those Phase I trials, doctors and investigators are also evaluating efficacy, is this drug working. But the primary goal of the early phase trial is actually to find the right dose to then study in larger groups. And so, if they find the right dose and there’s good biological rationale for the compound, then the trial would go on to a Phase II.

Which might be just what we call single arm Phase II study, where every patient is getting that experimental drug. And we monitor them to see, is the drug effective, or is it less effective than the standard of care? Or sometimes they’re what we call, randomized Phase II trials where patients are randomized to either get the experimental drug, or to get what the standard of care would be in that situation. I think a lot of people get afraid about the idea of a randomized trial because they’re afraid they’re going to be randomized to a placebo. And that is really not done in the metastatic setting, because it wouldn’t be ethical to give a patient with active cancer a placebo.

So, usually the randomization would be either to the study compound or to a standard of care drug. And then if things look good in a Phase II trial, then a Phase III study is done which is usually what the FDA requires to allow a drug to go on and be administered outside of a study for approval. And those Phase III trials tend to be larger studies that’re done in larger groups of patients with more statistical validity because of their size, to determine, is this drug really better than the standard.

Katherine:

Right. We have another question we received earlier, this one from Eileen. She asks, how will I know whether my treatment is working?

Dr. Meisel:

That’s a really good question. So, I think for patients who have symptoms from their cancer, they often will know the drug is working because their symptoms improve. Say if you have lung metastases and you are short of breath and your shortness of breath gets better. That’s a really good sign that the treatment is working. I would say that often what we are doing, and it depends a little bit on the regimen and what the patient is getting and how often they’re coming in.

But we’re checking labs as well and sometimes there are lab abnormalities when a patient is diagnosed with metastatic cancer that can then improve over time. So, for example, if someone has a heavy burden of bone involvement with breast cancer, there’s a lab value called the alkaline phosphatases that will often be elevated. If that starts elevated and comes down, that’s a really good sign. And some of their liver function tests that we check and if a patient has liver metastases, we often will see those come down if a patient is responding.

There are also, what we call tumor markers that we can check in patients with metastatic breast cancer. Those would be proteins in the blood basically that can be made by the breast cancer in abundance. And those are called CA27-29 and CA15-3. Some doctors check both of them. Some will just check one depending on which one their laboratory at their institution is running. But typically, I will check those at diagnosis of metastatic disease. And then if it’s elevated, I know it’s a good marker to follow for my patient. And then I’ll follow that monthly or every three weeks, depending on when the patient is coming in to see me.

And if I see that marker start to go down, it’s not an absolute, but it can be a good early indicator of improvement with the treatment. And then I think it varies a little bit from practice to practice and based on patient preference. But often there will be scans done when a patient is initially diagnosed to determine the extent of the disease. So, usually a CT scan of the chest and the abdomen and the pelvis or a PET scan, which some of you may have heard of. Either one of those is good.

And that can be done about every 12 weeks usually in the beginning, to make sure a patient is responding and once you feel confident that they are, those can be done sell frequently. So, I would say the scans and the lab work and then the patient’s overall condition are usually the way that we look to see, are we having a response or not.

Katherine:

We’ve talked about several key tests. Some patients may be confused about whether they’ve received these tests. So, what questions should they ask their physician to make sure they’re getting appropriate testing?

Dr. Meisel:

I think it’s probably useful because not everybody needs every test, and I think there are often things you hear about online or from friends or even in a webinar like this, and there may be a good reason why you haven’t had that particular test. So, I wouldn’t assume that if you haven’t had everything that we’ve talked about today even, that someone’s made a mistake or that you need that and aren’t getting it. But I would ask. I think it’s always helpful to know more, knowledge is power. And so, if you have never had a CT scan or a CA27-29 level or a genomic testing.

I think it’s not a bad thing if you’re curious about it, to just ask your treating team, “Hey, I heard about genomic testing, is there a reason I haven’t had that? Or have I had that?” Maybe you have, and they called it something else. I think it is complicated, but I think it helps to understand what you’ve had done and what you haven’t had done. And sometimes, asking about something like that may prompt the team to do things that my benefit you.

Katherine:

Before we wrap up, Dr. Meisel, how do you feel about the future of breast cancer research and what would you like patients to know?

Dr. Meisel:

Yeah, I think one of the most important things and I actually said this to a family this morning where a loved one had received a new diagnosis of metastatic breast cancer is that the field has evolved so much over the past five years. I think often when people get a diagnosis of metastatic breast cancer, it’s the most dreadful feeling they ever had. They remember that day for the rest of their lives. But we are seeing so many people do so well for so long now and tolerate treatments well because the treatments are better tolerated.

And there’s I think more attention being paid now to symptom management. That people really can do so much better than they’ve been doing. And I would say really, every year, even every six months, when I go to give a lecture on a topic in metastatic breast cancer, I can’t just give the same talk. I’m always having to update my slides because there’s so many new things coming out, so much new research on the table.

And we’re seeing so many new drug approvals now that we’re starting to unlock some of these new mutations and reasons for progression and understanding new drug classes. So, really think it is a bright time to be in breast cancer research, and there’s never been a better time to be a patient if you have to fall into that category.

Katherine:

It all sounds so promising, Dr. Meisel. Thank you so much for joining us today.

Dr. Meisel:

You’re so welcome. Thank you for having me.

Katherine:

And thank you to all of our partners. 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. Also, don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs.

To learn more about breast cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell, thanks for joining us.

 

What Are Biomarkers and How Do They Impact Lung Cancer Treatment Options?

What Are Biomarkers and How Do They Impact Lung Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

What are lung cancer biomarkers, and how do they impact treatment options? Dr. Isabel Preeshagul defines biomarkers and explains how different biomarkers may help determine treatment options and aid in predicting treatment response. 

Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul here.

See More From INSIST! Lung Cancer

Related Resources:


Transcript:

Katherine Banwell:

Well, let’s define a few terms that are often confusing for patients. What are biomarkers?

Dr. Preeshagul:

Those are somatic alterations in the tumor just like EGFR, or ALK fusions, or MET exon 14, or MET amplification, or KRAS G12C.

These are all genes that are altered in the tumor. And these are genes that drive the tumor to grow. There are also other markers like PD-L1, which is a marker for response to immunotherapy. And there are various markers.

I could go on and talk about it for hours, but those are the more common ones that we know how to treat and how to handle and prognosticate.

Katherine Banwell:

And another term that’s sometimes confusing, what is a genetic mutation?

Dr. Preeshagul:

So, for genetic mutations, you have germline, and you have somatic. So, a germline mutation may be something like a BRCA1 or a BRCA2 that we see in patients with breast cancer or prostate cancer versus a somatic mutation which would be EGFR that I had mentioned or ALK fusion. So, germline mutations are the ones that we worry about being heritable.

And somatic mutations are those that are not thought to be heritable but thought to happen spontaneously within the tumor itself and cause the tumor to grow. We are constantly learning more about these though, however. But it’s really important to talk with your doctor to see if you have a germline mutation or a somatic mutation or if you have both.

And it is never wrong to seek an opinion with a genetic counselor to make sure that everyone in your family is safe, that you’re up to date on age-appropriate cancer screening, and that your family gets screened appropriately as well if indicated.

Katherine Banwell:

Are there specific biomarkers that affect lung cancer treatment choices?

Dr. Preeshagul:

Oh, definitely. One that I had mentioned is PD-L1. And this is a marker that we look for expression. So, based on FDA approval for pembrolizumab, if you have an expression of 50 percent or more, you are able to get immunotherapy alone in the upfront setting. If you have less than 50 percent, we often give you chemotherapy plus immunotherapy. And that’s based on a clinical trial known as KEYNOTE-189.

Other markers such as EGFR, as I had mentioned, ALK fusions, RET, NTRK, MET exon 14, ROS1, KRAS, HER2, you name it, those are alterations that we look for ideally in the upfront setting as well and can really affect treatment planning.

And those patients that harbor mutations like EGFR and ALK and ROS1 or MET exon 14, we know that these patients do better with targeted therapy upfront, not standard-of-care chemo. So, it’s really important to know about the presence of these alterations before you start treatment if possible.