Tag Archive for: microsatellite instability

How Do Biomarker Test Results Impact Gastric Cancer Treatment Options?

How Do Biomarker Test Results Impact Gastric Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

Biomarker test results comprise one of several factors that impact gastric cancer treatment options. Dr. Yelena Janjigian explains biomarker testing, key gastric cancer biomarkers that affect care, and other factors that may impact treatment decisions. 

Dr. Yelena Janjigian is Chief of Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center. 

See More From INSIST! Gastric Cancer

Related Programs:

How Is Gastric Cancer Diagnosed and Staged?

How Is Gastric Cancer Diagnosed and Staged?

An Overview of Current Gastric Cancer Treatment Options

An Overview of Current Gastric Cancer Treatment Options

Gastric Cancer Treatment and Research Highlights

Gastric Cancer Treatment and Research Highlights


Transcript:

Katherine:

Dr. Janjigian, I’d like to talk about what goes into deciding on a best treatment for a patient. Is there testing that helps you understand a patient’s individual disease? 

Dr. Janjigian:

One is an important factor about this disease, and when the patient comes in, the number one factor that helps us decide, what treatment to assign, is how well is the patient feeling? What are their nutritional deficits? How functional they are. Are they able to tolerate the treatment? 

Because as an oncologist, the first rule is do no harm. Most patients come in when they’re first diagnosed are pretty well functional. They’re still able to eat. And so, they’re really up for the most aggressive. And that’s probably the number one wish I have from patients. I just want us to stay well and stay alive. So, we can be very aggressive with them, at least folks that come to see us in New York. And so, then the decision fork is really do you want only standard therapy, or are you interested in clinical trials? And I think what I am able to really explain to the patients, which is great, is that the benefit of trials – and, of course, you can never guarantee that a trial will be successful, right? Because that’s by definition – a clinical trial is experimental therapy.

But for gastric cancer and stomach cancer where we need as many treatment options as possible, a clinical trial gives you an opportunity to try something different, and then go back to standard therapy, and then try experimental therapy, and then go back to standard therapy.  

So, it gives you as many options as possible. The way that I help our patients visualize this is you’re trying to cross a very wide and somewhat turbulent river. And you need as many stepping stones as possible. And a clinical trial, if it makes sense for you and if you’re able to do it physically, it gives you that other option. The most important other factor is to understand which subset of stomach cancer you have, right? Because biomarker testing has helped us tremendously to advance this disease. If you look at and if you watch any of my talks, I usually have this timeline of therapeutic development in stomach cancer until really this past year.   

We’re 2022, 2021. There was over a decade of negative trials, right? And the reason why I think is because the design of the trial really focused on targeting all the patients the same way. And now the trials are becoming more and more sophisticated. So, when we talk about the biomarker testing of the tumor, the patient’s specific tumor.  

It’s important for the patient to ask their physician. “What is the status of my tumor?” And the four critical biomarkers are microsatellite instability, HER2, PD-L1, and Claudin-18.2. So, those four biomarkers have really helped us transform this field especially in patients with metastatic disease. And in all of the tertiary cancer centers, certainly here at Memorial Sloan Kettering,  for each of the subsets we have a full research portfolio.  

So the patients have both standard and experimental options available to them.             

Katherine:

Well, how can test results like biomarker testing affect the patient’s prognosis and treatment options? 

Dr. Janjigian:

It will depend on the treatment and how it is paired to the biomarkers. So, for example, a certain subset of tumors such as microsatellite and stable tumors are patients with PD-L1 high tumors or even patients with HER2-positive tumors. Now in clinical trials, we see that those patients have an outstanding dramatic response to combination therapies often with chemotherapy or immunotherapy together or even HER2 directed therapy with immunity therapy. So, it really will impact how likely your tumor is to shrink. And if the tumor is shrinking, and if you’re feeling better, obviously that translates to better survival.  

Katherine:

Yeah. What questions should patients be asking about their test results? 

Dr. Janjigian:

I think it’s important for patients to be very clear with their providers about their willingness to undergo repeated biopsies if needed.  

I think the number one misunderstanding or misnomer that I see when patients come in to see me as a highly trained specialists, and they’re seeking me out for expertise and second and third and fourth opinions is that when the biomarker test is not done, often the answer in the community from the physician was, “Well, there was insufficient tissue or the tissue quality was not great, and that’s we’re going to do it.

And it turns out the patient is perfectly willing and able to undergo a second biopsy. They really do not mind because a lot of times it’s just as simple as having a repeat endoscopy. Or even on treatment off and the problem is it’s a constantly evolving cancer. So, for example, if you receive first-line treatment and then you progressed and you need additional treatment, often it’s important to get a second biopsy to understand what your biomarkers are at that point. 

And I described this to my patients. We can’t get into a battle with outdated maps. We need to know. And sometimes when there’s a misunderstanding, the doctors think, “Maybe the patient wouldn’t be willing to do it. Or they are risk-averse.” And the patient’s more than willing to do it. So, I think communicating your wishes and your intent clearly with your doctors and not being shy to ask questions, and also not being shy to seek out clinical trials, right?

So, yesterday I was in clinic. I see a lot of this disease. I often see 30 patients at clinic. I had an 80-year-old patient in my clinic, right? And before you meet the patient, most doctors would think, “Well, it’s an elderly patient. They wouldn’t even be interested in clinical trials. What are we trying to accomplish here?” 

Katherine:

Right.  

Dr. Janjigian:

But this patient clearly is – he exercises five days a week. He’s extremely active. He wants the best options for him.  

So, I am not an ageist, so I asked him. I said, “What are your sort of goals of this therapy? And how interested are you in clinical trials?” And him and the family were extremely enthusiastic. And, “We’re going to go for it, and we’re going to try.” So, I think having those conversations with your doctors – because you remember gastric cancer is very rare.

In my clinic I see 30 patients, but in most normal sort of oncology practices, it’s lung, breast, and colon, the big three that sort of saturate the schedule of the oncologists. So, if they see one or two gastric cancers a month, they may not be thinking along the same lines of your disease. So, then you have to ask the questions of, “Are there any clinical trials? Should I see a specialist?” Did you do all of my biomarkers? 

Tools for Accessing Personalized Advanced Prostate Cancer Treatment and Care

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

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

See More From INSIST! Prostate Cancer

Related Resources

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

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

How Do Biomarker Test Results Impact Prostate Cancer Treatment Options

How Do Biomarker Test Results Impact Prostate Cancer Treatment Options

Essential Testing Following a Prostate Cancer Diagnosis

Essential Testing Following a Prostate Cancer Diagnosis 


Transcript:

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

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

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

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

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

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

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

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

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

Endometrial Cancer Treatment and Research Updates

Are there advances in endometrial cancer research that patients should know about? Expert Dr. Emily Ko shares updates about ongoing clinical trials, including immunotherapy and combination approaches, and discusses how endometrial cancer subtypes affect treatment options. 
 
Dr. Emily Ko is a gynecologic oncologist and Associate Professor of Obstetrics and Gynecology at the University of Pennsylvania. Learn more about Dr. Ko.

Related Programs:

What Should Endometrial Cancer Patients Know About Clinical Trials?

How Is Endometrial Cancer Staged?

How Is Endometrial Cancer Staged?

What Are Treatment Options for Endometrial Cancer?

What Are Treatment Options for Endometrial Cancer?


Transcript:

Katherine:

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

Dr. Ko:

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

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

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

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

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

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

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

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

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

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

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

Katherine:

Dr. Ko, are there other research or treatment advances that patients should know about? 

Dr. Ko:

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

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

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

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

Prostate Cancer Treatment: What Is Precision Oncology?

Prostate Cancer Treatment: What Is Precision Oncology? from Patient Empowerment Network on Vimeo.

How is precision oncology used in prostate cancer? Dr. David Wise defines precision oncology and explains how it is used in conjunction with prostate cancer testing for patient care.

Dr. David Wise is Director of Genitourinary Medical Oncology at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health. Learn more about Dr. Wise.

See More From INSIST! Prostate Cancer

Related Resources

How Can You Access Personalized Prostate Cancer Treatment?

How Can You Access Personalized Prostate Cancer Treatment?

How Does Genetic Testing Impact Prostate Cancer Care?

Are We Getting Closer to Precision Oncology for Prostate Cancer

Are We Getting Closer to Precision Oncology for Prostate Cancer


Transcript:

Dr. David Wise:

Absolutely. So, precision oncology is really a term that describes being able to tailor treatment to a patient’s cancer to the information that we have from that specific individual. So, it’s really tailored medicine. And it’s precise because, typically, that treatment is leveraging or exploiting a specific vulnerability or feature that we’re able to discern by a specialized testing of that patient’s cancer, okay?  

And so, everything that I’ve been discussing, biomarker testing that lends itself directly to treatment is largely overlapping and very much an example of precision oncology. So, using genetic test results to guide treatment from that patient, that’s tailored to that patient. So, that is precision oncology.  

Using that patient’s PSMA profile to determine the benefit of lutetium, that is, in my view, precision oncology. There are other examples of this in multiple different spheres and using multiple different treatment types, but that’s the general concept. I think the other example of precision oncology in general and specifically for prostate cancer are targeting NTRK mutations. So, NTRK I, II, and III, those are genes that can get mutated in any cancer type.   

And just like the example of immunotherapy with microsatellite instability, the same holds true. So, any cancer with an NTRK mutation, there is an FDA approval to use NTRK inhibitory oral medications to treat that patient. Similarly to immunotherapy and microsatellite instability, we wish those mutations were more common because the treatment is very well-tolerated and is incredibly effective.  

But still, just because it’s not common doesn’t mean we shouldn’t look for it because of how impactful these treatments can be. 

How Do Biomarker Test Results Impact Prostate Cancer Treatment Options?

How Do Biomarker Test Results Impact Prostate Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

What can biomarker test results indicate about prostate cancer treatment options? Dr. David Wise discusses genetic mutations, treatment classes, and testing methods that are commonly examined to help determine optimal prostate cancer approaches.

Dr. David Wise is Director of Genitourinary Medical Oncology at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health. Learn more about Dr. Wise.

See More From INSIST! Prostate Cancer

Related Resources

What Is a Prostate Cancer Biomarker

What Is a Prostate Cancer Biomarker?

Prostate Cancer Testing: What Tests Should You Advocate For?

How Do Biomarker Test Results Impact a Prostate Cancer Patient’s Prognosis

How Do Biomarker Test Results Impact a Prostate Cancer Patient’s Prognosis?


Transcript:

Dr. David Wise:

So, that’s a great question. So, there are multiple gene test results that can directly influence a choice of treatment. I think that it’s important to highlight two main categories, both within the genomic testing setting. Both of these test results have their major impact in patients with metastatic prostate cancer, whether the cancer has been treated already and is resistant to current treatments, or even some situations where the cancer has not even been treated.  

For metastatic prostate cancer, I think it’s important to assess whether the cancer has evidence of a BRCA1 or 2 mutation, or whether the cancer has evidence of a genetic feature called microsatellite instability, or MSI high. Cancers that have evidence of BRCA1 or 2 have clear benefit. Patients have clear benefit from treatment that targets those genes. And that’s a class of oral medications called PARP inhibitors, several of which are already FDA-approved for hormone-resistant metastatic prostate cancer with evidence of BRCA1 or 2 mutation.  

There are even newer clinical trials which are testing the use of those medicines at the outset of men who are initially diagnosed with metastatic prostate cancer, even naïve to treatment and testing whether we should be adding on PARP inhibitors for men with that genetic feature.  

Microsatellite instability, as well, leads to a clear FDA indication for immunotherapy with what we call checkpoint inhibitors that target and reinvigorate the body’s immune system. We know that prostate cancers with that particular genetic feature, which unfortunately is still an uncommon type of prostate cancer – but when it happens, it’s important to know about it because those immunotherapies can have truly life-changing, truly very long lasting, in the order of years, benefit to keeping that cancer to an undetectable level. Now, I would say, those are the key genomic features that directly translate to changes in treatment.  

There are other biomarkers, one we haven’t talked about which is very impactful, which is levels of PSMA expression on a PET scan. So, we talked about that in the setting of making a diagnosis, but it also is important for dictating best treatment. So, we now know, based on the results of a large Phase III trial that patients with prostate cancers that have PSMA uptake on PET imaging, which is an imaging biomarker, not a genetic biomarker, but an imaging biomarker.  

Those patients respond quite well to lutetium PSMA, which is a radioligand therapy that targets PSMA-producing prostate cancers. And so, those are examples of, I think, very impactful biomarkers that patients need to know about, so that they can ask their physicians to get tested to see if they’re candidates for those potential treatments.  

So, the genetic tests can be done either on biopsy material or on blood. And the latter has really been a major advance because we’ve been able to identify patients who are eligible without exposing them to an additional fresh biopsy. Sometimes, we need to because sometimes the blood does not have sufficient material to be able to establish the diagnosis. But still, it is often worth trying because, of course, we would try to do anything to avoid undergoing a risky procedure, and this is an example of that. In order to assess hereditary genetic risk, that can be done from a saliva sample. So, often, a cheek swab is enough, but testing for that is often pretty standard as well. So, that’s another option.  

So, in order to assess PSMA expression, which lends itself directly to the use of lutetium PSMA, that’s the straightforward PET scan. It’s now something that is readily available at the vast majority of academic centers and in the community as well.