Finding Actionable Biomarkers in Colorectal Cancer

Transcripts:John L. Marshall, MD: Tell me what’s going on with NCI-MATCH, and we’ll also talk a bit about TAPUR.

Daniel G. Haller, MD: TAPUR is an ASCO-based MATCH-like study.

John L. Marshall, MD: First ever trial by ASCO.

Daniel G. Haller, MD: It’s the first ever trial by ASCO, and there’s an Intergroup trial, as well. So, there are three large trials; some are called “baskets” and some called “buckets.” Basically, you screen tumors for every possible mutation. You try to find ones that you actually have a drug for where that’s actionable. What it requires is that the NCI, ASCO, or the Intergroup get at least five, six, or seven hopeful companies together so you actually have enough drugs to find enough patients. With the MATCH trial—Stan Huffman reported at the recent ECOG meeting—you’re finding very few actionable mutations.

John L. Marshall, MD: Is that why it shut down?

Daniel G. Haller, MD: It was on hold, in part, because they were overwhelmed with the volume. It’s back up again because they’ve overcome that problem.

John L. Marshall, MD: And you said this earlier, but in that trial, you have to do repeat biopsy, right? You have to send, not the old specimen, but a new one?

Daniel G. Haller, MD: In the Intergroup trial. I’m not sure in MATCH.

John L. Marshall, MD: No, MATCH you have to send new, for sure.

Cathy Eng, MD: Up to three biopsies, if I’m correct.

John L. Marshall, MD: Yes. And part of that frustration has been the samples get sent, and then you find out 3 weeks later that you didn’t have enough, right?

Tara E. Seery, MD: It takes 6 weeks to find out.

Cathy Eng, MD: I think the new mechanism is going to be in place, and it’s supposed to take up to 14 days.

John L. Marshall, MD: So, that’s MATCH. TAPUR is a little different. It’s more of a relationship directly with Pharma and approved drugs, like HER2-targeted therapies, where if you find one, they’ll get you the drugs in exchange for reporting the information. It is a clinical trial, but it’s a much simpler clinical trial—fewer data points and a lot less toxicity collection. But you get it and see if it worked or not. The hope is that that would ultimately extend indications, if we could prove that HER2 therapies work for colon cancer in the right place—and it extended indications.

Daniel G. Haller, MD: It’s going to get very complicated because we used to simplify things by saying that you treat the organ from which the tumor came. And then people said, “We’re going to totally change that; it’s only based on the genomic pattern.” But, between melanoma and colon cancer, BRAF mutations occur. In one, inhibitors work, and in the other, they don’t work by themselves—although they may with EGFR combination therapy. It’s more complex than we thought originally.

Cathy Eng, MD: Definitely.

John L. Marshall, MD: Part of my anxiety about all of this is that even with a nation, ASCO, and cooperative groups, for these rare mutations, we’re don’t have the bandwidth to answer some of these questions in a timely enough fashion. My midlife crisis has been we need it on an even larger scale on a global level. So, I’m really excited.

I think every institution at this table is represented in this. Some members of your groups—Peter, Stan, and Mayo—are trying to work together. We’ve got a collection of 35,000 new GI cancer cases around the world coming through the pipeline. If we can profile all of those, then that rare tumor…I always like the example of if I have a marker that’s only 10% of colon, BRAF or whatever. If I want a 50-patient study, I’ve got to screen 500 patients. If I want that in a year, that’s 40-some-odd patients per month I have to screen. No big center or cooperative group can really do that, so we need to collaborate. I’m really pleased that we’re moving that forward, and it’s like the TAPUR study in that it’s a collaboration between academia and industry.

Daniel G. Haller, MD: We’re speeding the process of biopsying and testing in the MATCH trial—at least in the initial group, where they, I think, need about 30 patients per mutation to get a sense of what would work or what would not work across tumor types. Most of these patients are not first- or second-line therapy; they’re not at all. A lot of patients were never treated because they progressed while they were being tested and waiting for the results and waiting for the drug. So, that has to be compressed into a very small timespan. Maybe it’s good that they fell off because maybe they shouldn’t have been treated.

Cathy Eng, MD: The good thing with MATCH is that now, instead of having 10 arms, they’re going to have 23 arms. That’s hopefully going to be a big advantage. And they reactivated the study 3 days ago.

Tara E. Seery, MD: They’re going to screen 5000 patients.

Cathy Eng, MD: They’re hoping for 20%….

John L. Marshall, MD: If I found a BRAF-positive patient, what should I do with him?

Cathy Eng, MD: If you have a BRAF-positive patient, refer them for a clinical trial.

John L. Marshall, MD: What’s hot right now?

Cathy Eng, MD: Well, the SWOG trial just closed.

John L. Marshall, MD: So, what have I got?

Cathy Eng, MD: There are some other trials that are under development, but I presume we’re going to have other clinical trials, as well.

John L. Marshall, MD: Combination therapy, EGFR plus inhibitors, and things.

Daniel G. Haller, MD: Remind me of the SWOG trial again.

Cathy Eng, MD: The SWOG trial was a randomized phase II study. The control arm was irinotecan with cetuximab as second-line. The investigation arm was with the addition of vemurafenib.

John L. Marshall, MD: Before we move on to managing metastatic disease, over the last couple of years, we’ve seen an emergence of categorizing colon cancer by different molecular profiles. We’re talking here at ASCO about how that reflects in anatomy. Is anybody here doing broader profiling yet to try to put them into one of the four molecular buckets that are out there, or is that not quite ready—the Tejpar analysis? Is anybody there yet?

Tanios Bekaii-Saab, MD: I don’t think that analysis is there yet for us to be there with it.

John L. Marshall, MD: Of how that would affect clinical?

Tanios Bekaii-Saab, MD: Yes. I think it still needs to be looked at in wider data sets and be confirmed before it makes sense. It could be just a prognostic bucket list, rather than actually help us direct what type of therapy. It’s useful, but I think more work needs to be done. For the day-to-day applicability, it’s not there yet.

John L. Marshall, MD: It’s here we’re going but we’re not sure how; where we’re going to be.

Tanios Bekaii-Saab, MD: We’re not sure where we’re going to be, right.

Cathy Eng, MD: Thought provoking.

John L. Marshall, MD: It is.

Transcript Edited for Clarity