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Broad Molecular Profiling in Colorectal Cancer

Panelists: John Marshall, MD, Lombardi Comprehensive Cancer Center; Alan P. Venook, MD, Helen Diller Family Comprehensive Cancer Center; Tanios Bekaii-Saab, MD, The Mayo Clinic; Johanna Bendell, MD, The Sarah Cannon Research Institute
Published: Wednesday, Mar 29, 2017



Transcript:

John Marshall, MD:
We talked about immune therapies and the future there. But I know everyone on this panel is excited about the concept of broad molecular profiling, finding other novel targets, the breakthroughs that Alan alluded to earlier. So, Johanna, when should we be doing broad profiling on patients? What utility does it have?

Johanna Bendell, MD: Personally, I do it when they’re first diagnosed with metastatic disease, where it’s non-curable. And so, I try to do what I call “one-stop shopping.” There are a lot of molecular profiling platforms that allow you to test multiple things at once with 1 tumor sample. So, you can get microsatellite instability, you can get expanded RAS, and you can get HER2 status because we’ve also seen recent data that, again, 5% of colorectal cancer patients with metastatic disease potentially have overexpression of HER2. And we’ve seen data with both trastuzumab/lapatinib and trastuzumab/pertuzumab showing nice and durable responses that we see for these patients. So, trying to pick them up, but also trying to collect this data. There’s a lot of big movement now to collate data from all of the molecular profiling that we’re doing on these patients to try to get more broad strokes about who’s going to respond. And then, also the potential some day for longitudinal molecular profiling. What changes along the way and is it the cause of these therapies or not, and how do we get a handle on that?

John Marshall, MD: You’re a policy guy, Alan. Should insurance cover broad profiling for our patients?

Alan P. Venook, MD: I think they should. But in return, there should be a way that they can be assured that these results will not be overinterpreted or misinterpreted. I think, to me, the flaw is not in the analysis, it’s in the application of the findings. So, you get some of these printouts that, say, recommend everolimus. And I think the answer is no. To me, though insurers should be covering it, I’m hard-pressed to see how they can demand that we have proven results and benefits of the testing if they don’t allow, if they don’t cover the testing in the first place as much as they did decades ago with bone marrow transplant for breast cancer. I think if we could deliver on making sure that these are not overinterpreted, that would be a big difference maker. And I think the other thing we’re doing, of course, in academic centers, is doing serial analyses to see what the changes are. That’s a research tool, of course.

John Marshall, MD: I’m doing this, too, through our national collaboration. And the more I’m doing this, the more I’m seeing RAS change. And so, should we be re-biopsying patients like they’re doing in lung cancer? Like they’re doing in breast cancer?

Tanios Bekaii-Saab, MD: Well, I think the cost of the free biopsy is certainly interesting. I’m hoping that ultimately the liquid biopsies are going to become the standard in this field and will actually afford us with the opportunity to have a real-time view. Colorectal cancer is one of those cancers on the top of shedding, circulating DNA to the circulation, so it’s actually a good target disease for liquid biopsy and is essentially looking at the molecular and genetic changes in real time through a blood draw rather than putting a needle in the liver.

John Marshall, MD: We’re all hoping that’s true. From what I know today, you can do a liquid biopsy on these patients, but I understand that with their tissue correlates, I’m not relying on it.

Tanios Bekaii-Saab, MD: Yes and no. They’re reasonable. Actually, there’s a poster presented at ASCO GI that actually shows very close correlation. You do depict, for example, more EGFR mutations when you correlate older tissue. But we know from re-biopsying tissue that a number of these actually do change with time under selective pressure from EGFR inhibitor application. So, I think the tools need to be refined, and they are being refined, but I do think there is some level of utility.

John Marshall, MD: It’s not crazy to think about re-biopsy. I think I agree with you, Johanna, that I want one-stop shopping. So, if I’m going to do my MSI, and RAS, and BRAF, what the heck, let’s just do it all right now and know. But let’s say it’s 2 years later and I got a big liver metastasis I can get a piece of.

Johanna Bendell, MD: Yes, so I do it in context of clinical trials. You’re doing it as part of research because that’s mostly what you’re going to find in those changes that would change your treatment pattern at that point in time. But, if you have a reason that that result is going to change what you’re going to do, whether it be clinical trial or your practice, then I think it’s reasonable to do it.

Transcript Edited for Clarity

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Transcript:

John Marshall, MD:
We talked about immune therapies and the future there. But I know everyone on this panel is excited about the concept of broad molecular profiling, finding other novel targets, the breakthroughs that Alan alluded to earlier. So, Johanna, when should we be doing broad profiling on patients? What utility does it have?

Johanna Bendell, MD: Personally, I do it when they’re first diagnosed with metastatic disease, where it’s non-curable. And so, I try to do what I call “one-stop shopping.” There are a lot of molecular profiling platforms that allow you to test multiple things at once with 1 tumor sample. So, you can get microsatellite instability, you can get expanded RAS, and you can get HER2 status because we’ve also seen recent data that, again, 5% of colorectal cancer patients with metastatic disease potentially have overexpression of HER2. And we’ve seen data with both trastuzumab/lapatinib and trastuzumab/pertuzumab showing nice and durable responses that we see for these patients. So, trying to pick them up, but also trying to collect this data. There’s a lot of big movement now to collate data from all of the molecular profiling that we’re doing on these patients to try to get more broad strokes about who’s going to respond. And then, also the potential some day for longitudinal molecular profiling. What changes along the way and is it the cause of these therapies or not, and how do we get a handle on that?

John Marshall, MD: You’re a policy guy, Alan. Should insurance cover broad profiling for our patients?

Alan P. Venook, MD: I think they should. But in return, there should be a way that they can be assured that these results will not be overinterpreted or misinterpreted. I think, to me, the flaw is not in the analysis, it’s in the application of the findings. So, you get some of these printouts that, say, recommend everolimus. And I think the answer is no. To me, though insurers should be covering it, I’m hard-pressed to see how they can demand that we have proven results and benefits of the testing if they don’t allow, if they don’t cover the testing in the first place as much as they did decades ago with bone marrow transplant for breast cancer. I think if we could deliver on making sure that these are not overinterpreted, that would be a big difference maker. And I think the other thing we’re doing, of course, in academic centers, is doing serial analyses to see what the changes are. That’s a research tool, of course.

John Marshall, MD: I’m doing this, too, through our national collaboration. And the more I’m doing this, the more I’m seeing RAS change. And so, should we be re-biopsying patients like they’re doing in lung cancer? Like they’re doing in breast cancer?

Tanios Bekaii-Saab, MD: Well, I think the cost of the free biopsy is certainly interesting. I’m hoping that ultimately the liquid biopsies are going to become the standard in this field and will actually afford us with the opportunity to have a real-time view. Colorectal cancer is one of those cancers on the top of shedding, circulating DNA to the circulation, so it’s actually a good target disease for liquid biopsy and is essentially looking at the molecular and genetic changes in real time through a blood draw rather than putting a needle in the liver.

John Marshall, MD: We’re all hoping that’s true. From what I know today, you can do a liquid biopsy on these patients, but I understand that with their tissue correlates, I’m not relying on it.

Tanios Bekaii-Saab, MD: Yes and no. They’re reasonable. Actually, there’s a poster presented at ASCO GI that actually shows very close correlation. You do depict, for example, more EGFR mutations when you correlate older tissue. But we know from re-biopsying tissue that a number of these actually do change with time under selective pressure from EGFR inhibitor application. So, I think the tools need to be refined, and they are being refined, but I do think there is some level of utility.

John Marshall, MD: It’s not crazy to think about re-biopsy. I think I agree with you, Johanna, that I want one-stop shopping. So, if I’m going to do my MSI, and RAS, and BRAF, what the heck, let’s just do it all right now and know. But let’s say it’s 2 years later and I got a big liver metastasis I can get a piece of.

Johanna Bendell, MD: Yes, so I do it in context of clinical trials. You’re doing it as part of research because that’s mostly what you’re going to find in those changes that would change your treatment pattern at that point in time. But, if you have a reason that that result is going to change what you’re going to do, whether it be clinical trial or your practice, then I think it’s reasonable to do it.

Transcript Edited for Clarity
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