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Considering the Basics in Newly Diagnosed mCRC

Insights From: John L. Marshall, MD, MedStar Georgetown University Hospital; Tanios S. Bekaii-Saab, MD, Mayo Clinic
Published: Friday, Mar 29, 2019



Transcript: 

John L. Marshall, MD:
Welcome to this OncLive News Network® webinar. Today’s discussion will be focused on a practical approach to treatment of metastatic colorectal cancer. I’m your host, Dr John Marshall, chief of the Division of Hematology/Oncology at MedStar Georgetown University Hospital, professor of medicine and oncology at the Lombardi Comprehensive Cancer Center, and the director of the Ruesch Center for the Cure of GI [Gastrointestinal] Cancers in Washington, DC.

Today I’m joined by my very good friend and colleague Dr Tanios Saab, who’s a professor of medicine and senior associate consultant, the Division of Hematology and Oncology in the Department of Internal Medicine at the Mayo Clinic in Scottsdale/Phoenix, Arizona. During the next 60 minutes the 2 of us are going to navigate through some of the questions surrounding how we take care of and treat advanced colorectal cancer. We’re going to consider how we are using available agents, how they can be sequenced through the disease continuum, and how the latest data will help us in making these decisions in our clinics going forward, and hope it will help you as well.

So Tony, let’s really drill down together on, you’ve got a new patient walking in the door, you’ve got your stack of records—molecular medicine, precision medicine, how important is that? Do you need that right from the get-go? And if so, how do you get it?

Tanios S. Bekaii-Saab, MD: I definitely need that. We all definitely need that from the get-go. It is such an important factor in establishing the first discussion with the patient including understanding the continuum of care, and in some cases also of course it does affect what we do in the first line. So I think there are some basic essentials that we have to think about.

John L. Marshall, MD: Do you see it kind of, everybody’s doing it? Or … we see a lot of referral business.

Tanios S. Bekaii-Saab, MD: I see more and more.

John L. Marshall, MD: Yes.

Tanios S. Bekaii-Saab, MD: I see more and more, it’s interesting…. I’ve seen actually proactively a lot of our community oncology colleagues expanding on next-generation sequencing platforms. So not just the KRAS or the NRAS, but they’re really doing the whole thing, which is great. Unfortunately, there are still some small pockets where I see a patient with only KRAS, nothing else. But I think we’re in much better shape than where we were before in terms of doing this more widely.

John L. Marshall, MD: Yes, a lot of our patients, their first diagnosis was the colonoscopic alligator clip biopsy. And the [laboratories] that those go to are often reference labs for gastroenterologists. And they seem to be fairly consistently doing some measure of MSI [microsatellite instability], immunohistochemistry, or even some gene sequences. So I’m seeing that pretty consistently. But you and I have talked about this before. I think the language around this is really confusing and the print’s always so small it’s painful, and so I don’t know if you share this, but it’s sometimes difficult to figure out what the report actually is saying.

Tanios S. Bekaii-Saab, MD: It is sometimes difficult and now you have these little boxes—there’s a lack of benefit, or benefit—and it gets confusing what’s positive, what’s negative, what’s lacking, what’s not. And then to fish for these; when I read the report, the surgical pathology report that includes these proteins, whether they’re absent or present or what it means, it can get confusing. A lot of my Fellows get confused reading it. They don’t know if it’s positive, it’s negative, it means the patient has MSI-high or has potentially Lynch [syndrome]. I hope there will be a better way for us to make this more friendly.

John L. Marshall, MD: I still see pathologists putting in their notes, that this looks like MSI because it’s an inflamed tumor or something like that. And there are Fellows, of course, not necessarily knowing better, who might interpret it that way.

Tanios S. Bekaii-Saab, MD: Yes.

John L. Marshall, MD: So it’s important for us to know that.

Tanios S. Bekaii-Saab, MD: Absolutely.

John L. Marshall, MD: And so MSI, yes. And we’re sending off usually right from the beginning doing broad molecular profiling. You the same?

Tanios S. Bekaii-Saab, MD: As we should, yes, absolutely.

John L. Marshall, MD: Isn’t it research? I’m in this fight too about, OK, I need to know RAS, I need to know MSI, we need to know BRAF, HER2. But then isn’t everything else, we get criticized a lot, that everything else is research.

Tanios S. Bekaii-Saab, MD: You know, yes and no. Because let’s think about today, the NTRK fusions and their importance and essentially getting us to entrectinib, which has shown some significant and amazing results in some patients. Two years ago we didn’t understand what these mean, most of us didn’t. What does an NTRK fusion mean, if it’s there, and from this they didn’t test widely for it. And then the second thing is, of course, that now this drug is available, this agent is available, and if we haven’t done an expanded analysis, we’re going to have to go fish for more tissue … if we find it, if it’s still good, if there’s still enough of it, and then go back and see if we [can] retest. Meanwhile, the patient is anxious, progressing, and the yield is incredibly low. So we’re adding so much to the anxiety of our patients. We didn’t have those answers as soon as possible. Same for HER2, same for BRAF. Now it becomes even more important when we talk about HER2 and BRAF as it affects our first line. The other thing, I’m not sure it’s actually cheaper to do just the targeted versus the expanded.

John L. Marshall, MD: The old chem-20 versus a chem-70 asyndetic phos or something.

Tanios S. Bekaii-Saab, MD: Yes, exactly. I’m not sure it’s even cheaper. So if it’s not going to be cheaper, which I don’t think it is, and it’s not going to give us all the answers we’re looking for, which oftentimes it misses a couple that are important. And then the third aspect is we are having more and more of these precision medicine directed trials that are being made available to our patients. And not understanding what’s driving or what may be a potential driver for the tumor means that the patient will miss out on some of these opportunities that we know, now more and more, many of them are leading to fantastic results.


Transcript Edited for Clarity
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Transcript: 

John L. Marshall, MD:
Welcome to this OncLive News Network® webinar. Today’s discussion will be focused on a practical approach to treatment of metastatic colorectal cancer. I’m your host, Dr John Marshall, chief of the Division of Hematology/Oncology at MedStar Georgetown University Hospital, professor of medicine and oncology at the Lombardi Comprehensive Cancer Center, and the director of the Ruesch Center for the Cure of GI [Gastrointestinal] Cancers in Washington, DC.

Today I’m joined by my very good friend and colleague Dr Tanios Saab, who’s a professor of medicine and senior associate consultant, the Division of Hematology and Oncology in the Department of Internal Medicine at the Mayo Clinic in Scottsdale/Phoenix, Arizona. During the next 60 minutes the 2 of us are going to navigate through some of the questions surrounding how we take care of and treat advanced colorectal cancer. We’re going to consider how we are using available agents, how they can be sequenced through the disease continuum, and how the latest data will help us in making these decisions in our clinics going forward, and hope it will help you as well.

So Tony, let’s really drill down together on, you’ve got a new patient walking in the door, you’ve got your stack of records—molecular medicine, precision medicine, how important is that? Do you need that right from the get-go? And if so, how do you get it?

Tanios S. Bekaii-Saab, MD: I definitely need that. We all definitely need that from the get-go. It is such an important factor in establishing the first discussion with the patient including understanding the continuum of care, and in some cases also of course it does affect what we do in the first line. So I think there are some basic essentials that we have to think about.

John L. Marshall, MD: Do you see it kind of, everybody’s doing it? Or … we see a lot of referral business.

Tanios S. Bekaii-Saab, MD: I see more and more.

John L. Marshall, MD: Yes.

Tanios S. Bekaii-Saab, MD: I see more and more, it’s interesting…. I’ve seen actually proactively a lot of our community oncology colleagues expanding on next-generation sequencing platforms. So not just the KRAS or the NRAS, but they’re really doing the whole thing, which is great. Unfortunately, there are still some small pockets where I see a patient with only KRAS, nothing else. But I think we’re in much better shape than where we were before in terms of doing this more widely.

John L. Marshall, MD: Yes, a lot of our patients, their first diagnosis was the colonoscopic alligator clip biopsy. And the [laboratories] that those go to are often reference labs for gastroenterologists. And they seem to be fairly consistently doing some measure of MSI [microsatellite instability], immunohistochemistry, or even some gene sequences. So I’m seeing that pretty consistently. But you and I have talked about this before. I think the language around this is really confusing and the print’s always so small it’s painful, and so I don’t know if you share this, but it’s sometimes difficult to figure out what the report actually is saying.

Tanios S. Bekaii-Saab, MD: It is sometimes difficult and now you have these little boxes—there’s a lack of benefit, or benefit—and it gets confusing what’s positive, what’s negative, what’s lacking, what’s not. And then to fish for these; when I read the report, the surgical pathology report that includes these proteins, whether they’re absent or present or what it means, it can get confusing. A lot of my Fellows get confused reading it. They don’t know if it’s positive, it’s negative, it means the patient has MSI-high or has potentially Lynch [syndrome]. I hope there will be a better way for us to make this more friendly.

John L. Marshall, MD: I still see pathologists putting in their notes, that this looks like MSI because it’s an inflamed tumor or something like that. And there are Fellows, of course, not necessarily knowing better, who might interpret it that way.

Tanios S. Bekaii-Saab, MD: Yes.

John L. Marshall, MD: So it’s important for us to know that.

Tanios S. Bekaii-Saab, MD: Absolutely.

John L. Marshall, MD: And so MSI, yes. And we’re sending off usually right from the beginning doing broad molecular profiling. You the same?

Tanios S. Bekaii-Saab, MD: As we should, yes, absolutely.

John L. Marshall, MD: Isn’t it research? I’m in this fight too about, OK, I need to know RAS, I need to know MSI, we need to know BRAF, HER2. But then isn’t everything else, we get criticized a lot, that everything else is research.

Tanios S. Bekaii-Saab, MD: You know, yes and no. Because let’s think about today, the NTRK fusions and their importance and essentially getting us to entrectinib, which has shown some significant and amazing results in some patients. Two years ago we didn’t understand what these mean, most of us didn’t. What does an NTRK fusion mean, if it’s there, and from this they didn’t test widely for it. And then the second thing is, of course, that now this drug is available, this agent is available, and if we haven’t done an expanded analysis, we’re going to have to go fish for more tissue … if we find it, if it’s still good, if there’s still enough of it, and then go back and see if we [can] retest. Meanwhile, the patient is anxious, progressing, and the yield is incredibly low. So we’re adding so much to the anxiety of our patients. We didn’t have those answers as soon as possible. Same for HER2, same for BRAF. Now it becomes even more important when we talk about HER2 and BRAF as it affects our first line. The other thing, I’m not sure it’s actually cheaper to do just the targeted versus the expanded.

John L. Marshall, MD: The old chem-20 versus a chem-70 asyndetic phos or something.

Tanios S. Bekaii-Saab, MD: Yes, exactly. I’m not sure it’s even cheaper. So if it’s not going to be cheaper, which I don’t think it is, and it’s not going to give us all the answers we’re looking for, which oftentimes it misses a couple that are important. And then the third aspect is we are having more and more of these precision medicine directed trials that are being made available to our patients. And not understanding what’s driving or what may be a potential driver for the tumor means that the patient will miss out on some of these opportunities that we know, now more and more, many of them are leading to fantastic results.


Transcript Edited for Clarity
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