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Tissue-Based Testing Versus Liquid Biopsy in 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: You and I don’t necessarily agree completely on this, or we come at it from different angles. Tissue-based testing versus liquid testing. And there are a lot of people coming and knocking on all of our doors saying they’ve got the best test. And it’s really an amazingly rapidly evolving field, and I have to say I really want a liquid biopsy to do the job. You know, I haven’t really gone there yet; in colorectal and other diseases, I get it. And I know you kind of come at it from the other way, that you’re optimistic that this is going to be an impact. Are you using that in any way routinely for patients?

Tanios S. Bekaii-Saab, MD: The clear answer is, not as routine. I would think from the practical standpoint, you have those patients who come to you, you don’t have enough tissue, or you have issues, and you want to take the decision on the spot—think about your next patient with peritoneal carcinomatosis. And you think they may, they’re behaving like BRAF, but you don’t have the tissue and no one has done that BRAF. Within 6 days you can get your answer.

Now, as with the lung cancers, our lung cancer colleagues, we understand that the presence of an alteration means it’s present in the tissue. If it’s absent, you can’t definitely say that it’s not; then you have to rely on the tissue. But if I see a BRAF V600E mutation in the circulating free DNA, then I know the patient has circulating DNA. That’s about 70% to 80% likelihood of a match between the 2.

And so sometimes, and I’ve done that in a patient recently where I just, for the love of God, I couldn’t find that that tissue, we couldn’t get it released, and I didn’t have that answer. Guess what the patient was? V600E. So the patient went on FOLFIRINOX [fluorouracil/irinotecan/oxaliplatin]. Within less than a week I was able to get that answer.

The other place that I see this useful, and again, perhaps not yet in clinical practice, is to follow up certain clones, clonal expansions, specifically RAS and others, because it does me 2 things. One, we can understand when that emergence of resistance may happen. And the second is that whole concept of free challenge, where you may be able to reuse these EGFR inhibitors with about 20%-plus response rate when you see these RAS wild-type reemerging clones.

So I think it has some utility. I still think the tissue is the gold standard if you have enough of it and you’re able to take your decision on the spot. When I do a liquid-based [test] immediately, it’s usually because I know the patient may be eligible for follow up and maybe for trials, or when the tissue is not available.

John L. Marshall, MD: Let’s skip to the end maybe a little bit because I know you’re working very hard to run a study called COLOMATE, which is a sort of basket precision medicine and we’re very pleased to be helping and part of that. There you’re going to really look at this issue of liquid versus tissue, but liquid biopsies would get you into that study, too.

Tanios S. Bekaii-Saab, MD: And tissue as well.

John L. Marshall, MD: And tissue.

Tanios S. Bekaii-Saab, MD: So both, but everyone will have both. So if you think about it, it’s 1 house, 2 points of entry, and you don’t know which 1 is the better point of entry. They may be the same, they may get you to the same place, or 1 might get you in faster or what have you. So we’re going to compare the 2, but you get to the same point, which is essentially, it’s almost a basket, or bucket trials. And they have different names; they use platform, bucket, basket.

The point is that we’re thinking about where do these patients fit. So there’s for HER2 or RAS mutated, FGFR altered, and an EGFR rechallenge arm. And the number of arms, and these are dynamic, you’re a big part of that study. So that study will help us understand, one, whether we can truly match patients in colorectal cancer to a specific targeted agent when we find the target. And the second element is establishing the role of these liquid biopsies in a perspective fashion with tissue control. Thousands of patients will likely be on that study over the next few years, so that’s an exciting point.


Transcript Edited for Clarity
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Transcript: 

John L. Marshall, MD: You and I don’t necessarily agree completely on this, or we come at it from different angles. Tissue-based testing versus liquid testing. And there are a lot of people coming and knocking on all of our doors saying they’ve got the best test. And it’s really an amazingly rapidly evolving field, and I have to say I really want a liquid biopsy to do the job. You know, I haven’t really gone there yet; in colorectal and other diseases, I get it. And I know you kind of come at it from the other way, that you’re optimistic that this is going to be an impact. Are you using that in any way routinely for patients?

Tanios S. Bekaii-Saab, MD: The clear answer is, not as routine. I would think from the practical standpoint, you have those patients who come to you, you don’t have enough tissue, or you have issues, and you want to take the decision on the spot—think about your next patient with peritoneal carcinomatosis. And you think they may, they’re behaving like BRAF, but you don’t have the tissue and no one has done that BRAF. Within 6 days you can get your answer.

Now, as with the lung cancers, our lung cancer colleagues, we understand that the presence of an alteration means it’s present in the tissue. If it’s absent, you can’t definitely say that it’s not; then you have to rely on the tissue. But if I see a BRAF V600E mutation in the circulating free DNA, then I know the patient has circulating DNA. That’s about 70% to 80% likelihood of a match between the 2.

And so sometimes, and I’ve done that in a patient recently where I just, for the love of God, I couldn’t find that that tissue, we couldn’t get it released, and I didn’t have that answer. Guess what the patient was? V600E. So the patient went on FOLFIRINOX [fluorouracil/irinotecan/oxaliplatin]. Within less than a week I was able to get that answer.

The other place that I see this useful, and again, perhaps not yet in clinical practice, is to follow up certain clones, clonal expansions, specifically RAS and others, because it does me 2 things. One, we can understand when that emergence of resistance may happen. And the second is that whole concept of free challenge, where you may be able to reuse these EGFR inhibitors with about 20%-plus response rate when you see these RAS wild-type reemerging clones.

So I think it has some utility. I still think the tissue is the gold standard if you have enough of it and you’re able to take your decision on the spot. When I do a liquid-based [test] immediately, it’s usually because I know the patient may be eligible for follow up and maybe for trials, or when the tissue is not available.

John L. Marshall, MD: Let’s skip to the end maybe a little bit because I know you’re working very hard to run a study called COLOMATE, which is a sort of basket precision medicine and we’re very pleased to be helping and part of that. There you’re going to really look at this issue of liquid versus tissue, but liquid biopsies would get you into that study, too.

Tanios S. Bekaii-Saab, MD: And tissue as well.

John L. Marshall, MD: And tissue.

Tanios S. Bekaii-Saab, MD: So both, but everyone will have both. So if you think about it, it’s 1 house, 2 points of entry, and you don’t know which 1 is the better point of entry. They may be the same, they may get you to the same place, or 1 might get you in faster or what have you. So we’re going to compare the 2, but you get to the same point, which is essentially, it’s almost a basket, or bucket trials. And they have different names; they use platform, bucket, basket.

The point is that we’re thinking about where do these patients fit. So there’s for HER2 or RAS mutated, FGFR altered, and an EGFR rechallenge arm. And the number of arms, and these are dynamic, you’re a big part of that study. So that study will help us understand, one, whether we can truly match patients in colorectal cancer to a specific targeted agent when we find the target. And the second element is establishing the role of these liquid biopsies in a perspective fashion with tissue control. Thousands of patients will likely be on that study over the next few years, so that’s an exciting point.


Transcript Edited for Clarity
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