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Current State of Molecular Testing for Metastatic CRC

Insights From: Alan Venook, MD, University of California San Francisco ; John L. Marshall, MD, Georgetown University ; Mark Kozloff, MD, Ingalls Cancer Care; Richard Kim, MD, Moffitt Cancer Center
Published: Monday, Oct 22, 2018



Transcript: 

Alan Venook, MD: I’d like to say we are making more progress than we actually are in advanced colorectal cancer. Some diseases have been amenable to a personalized approach. There are actionable mutations or diseases that we’ve been able to get a good grasp on, and immunotherapies may work very well. In truth, for colon cancer or advanced colorectal cancer, progress has really been stymied over the last couple of years. We have a couple of targets and have certainly made a difference in some patients, but we’re leaving many patients behind, so I’d say we’re frustrated. Some of our most recent efforts in research have not led to the results that we were hoping to see, so I’d have to admit to being disappointed in our progress so far.

The extent of testing—the molecular testing of patients with colon cancer—is really a good question. It’s a debatable issue. Next-generation sequencing with a large platform will mostly give you a lot of background noise. In truth, at least so far, we really only need information on a few genes. So it’s tempting to say “Let’s do next-generation sequencing” or “Let’s do a very broad platform to get a lot of information,” but, in fact, very little of that will be helpful. My own belief is that we should be obtaining RAS status and BRAF status, if the KRAS is wild-type. And then, MSI status—microsatellite instability status. Although there are curiosities, there may be other things that you could do. In general, a full platform will probably be wasteful and won’t help you very much in making decisions.

You cannot have a BRAF mutation unless you’re KRAS wild-type, so some centers will send off a KRAS test first. If that turns up wild-type, they will then send off a BRAF test, which adds up in time. So, there are those limitations. Some centers do it themselves; others send it out. It depends on the turnaround time. In general, for most decision making, it’s not really an impediment. I think it really takes a week or 10 days. In extreme cases—let’s say with a large platform like FoundationOne—it could take 2 to 3 weeks. However, it’s better to make the best decision rather than to rush in—although, for many patients, it’s hard to be waiting around. We do them in-house—the RAS, MSI, and BRAF testing. We can do that within 4 or 5 days.

One of the big mistakes is not having enough tissue to get to do that. These days, many patients have metastatic disease. At presentation, there may be a little biopsy taken in the colon of the primary cancer. You start treatment or get things going. Then, lo and behold, you don’t have enough tissue. That’s a problem, so you have to make sure that you have enough tissue to get the test results.

Transcript Edited for Clarity 
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Transcript: 

Alan Venook, MD: I’d like to say we are making more progress than we actually are in advanced colorectal cancer. Some diseases have been amenable to a personalized approach. There are actionable mutations or diseases that we’ve been able to get a good grasp on, and immunotherapies may work very well. In truth, for colon cancer or advanced colorectal cancer, progress has really been stymied over the last couple of years. We have a couple of targets and have certainly made a difference in some patients, but we’re leaving many patients behind, so I’d say we’re frustrated. Some of our most recent efforts in research have not led to the results that we were hoping to see, so I’d have to admit to being disappointed in our progress so far.

The extent of testing—the molecular testing of patients with colon cancer—is really a good question. It’s a debatable issue. Next-generation sequencing with a large platform will mostly give you a lot of background noise. In truth, at least so far, we really only need information on a few genes. So it’s tempting to say “Let’s do next-generation sequencing” or “Let’s do a very broad platform to get a lot of information,” but, in fact, very little of that will be helpful. My own belief is that we should be obtaining RAS status and BRAF status, if the KRAS is wild-type. And then, MSI status—microsatellite instability status. Although there are curiosities, there may be other things that you could do. In general, a full platform will probably be wasteful and won’t help you very much in making decisions.

You cannot have a BRAF mutation unless you’re KRAS wild-type, so some centers will send off a KRAS test first. If that turns up wild-type, they will then send off a BRAF test, which adds up in time. So, there are those limitations. Some centers do it themselves; others send it out. It depends on the turnaround time. In general, for most decision making, it’s not really an impediment. I think it really takes a week or 10 days. In extreme cases—let’s say with a large platform like FoundationOne—it could take 2 to 3 weeks. However, it’s better to make the best decision rather than to rush in—although, for many patients, it’s hard to be waiting around. We do them in-house—the RAS, MSI, and BRAF testing. We can do that within 4 or 5 days.

One of the big mistakes is not having enough tissue to get to do that. These days, many patients have metastatic disease. At presentation, there may be a little biopsy taken in the colon of the primary cancer. You start treatment or get things going. Then, lo and behold, you don’t have enough tissue. That’s a problem, so you have to make sure that you have enough tissue to get the test results.

Transcript Edited for Clarity 
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