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Management of NTRK Fusions in CRC

Panelists: Howard Hochster, MD, FACP, Rutgers Cancer Institute; Joleen Hubbard, MD, Mayo Clinic; Christopher Lieu, MD, University of Colorado School of Medicine; John Marshall, MD, Georgetown University Hospital; Tony Saab, MD, Mayo Clinic
Published: Thursday, Mar 07, 2019



Transcript: 

John L. Marshall, MD:
Let’s shift gears just a little bit. Let’s go fishing. Ever caught an NTRK fusion?

Tanios S. Bekaii-Saab, MD: One.

John L. Marshall, MD: One? You caught 1. Was it a big one or?

Tanios S. Bekaii-Saab, MD: Medium sized.

John L. Marshall, MD: So what we’re talking about here is rare molecular abnormalities. But if you have one, we have medicines now that are very effective. So it changes how we practice.

Tanios S. Bekaii-Saab, MD: It changes how we practice somewhat. I’d say this is not MSI [microsatellite instability]-high and PD-1 [programmed cell death protein 1] inhibitors, but you do see some pretty amazing….

John L. Marshall, MD: I would argue it’s better than. If you have one of these, the response rate is 80%, 90% and with long durable responses.

Tanios S. Bekaii-Saab, MD: For some.

John L. Marshall, MD: Yeah.

Tanios S. Bekaii-Saab, MD: There’s still a question as to whether these responses are going to continue to be solid. With PD-1 inhibitors and MSI, we have 2, 3, 4 years follow-up.

John L. Marshall, MD: But on only 50%, 60% of the people.

Tanios S. Bekaii-Saab, MD: Absolutely. Now I like this. This reinforces the fact that I think that every single patient today with colorectal cancer [CRC], and perhaps all other cancers but at least with colorectal cancer, should get NGS [next-generation sequencing] or a platform that will include these NTRK fusions and other findings. Because as you’ve heard, we have all these good things—MSI, HER2, KRAS, BRAF, NRAS. And I think NTRK should go into that.

John L. Marshall, MD: How do we make sure we know we’re getting this when we order the testing?

Howard S. Hochster, MD, FACP: Right. Well that’s a question, especially if people got Foundation [Medicine] sequencing a little while ago. Those fusions weren’t in there* (see editor's note). So you have to go back.

John L. Marshall, MD: Even the current one doesn’t have all of the NTRKs* (see editor's note).

Howard S. Hochster, MD, FACP: Right. The current FDA approved Foundation panel doesn’t have all of that* (see editor's note). So it is a little bit of a question. It means going back and reading the fine print of what was actually tested for, which we tend to skip. You may need to put on your reading glasses or something like that. But it is worthwhile to make sure that this is tested for, and I think you need to make sure, on your Foundation request, that it is on there.

Tanios S. Bekaii-Saab, MD: Yes. And I think we’re talking about 0.3% to 0 .7% of the patients. But think about it like this. You have 100 patients coming to your clinic. If you don’t test every single one of them, you’re not going to capture that 1. So I think that’s why it’s very important, even more importantly for the lower yield alterations, that patients get access to these tests and eventually to these agents. I’m pretty impressed with the results. I can tell you, in pancreas cancer, you know we’ve seen some data from Mike Pishvaian, MD, PhD, on one of his patients. It’s short of amazing. And these are fantastic responses that we see. This is also a positive predictive biomarker. It really is 1-on-1, unlike a lot of the biomarkers we have in colorectal cancer.

John L. Marshall, MD: I think one of our struggles will be if we don’t have adequate tissue, is something like this, a 1% or under 1% return, worth biopsying? And I think you have to make an individual decision.

Tanios S. Bekaii-Saab, MD: I’d say the answer is, yes. The liquid biopsy component is being refined. It’s still too early. It could be a good alternative in case you don’t have tissue. But right now, I would actually rebiopsy patients. Because it’s not just this NTRK. If you don’t have tissue for NTRK, you probably don’t have tissue for HER2 and others. So I think you should rebiopsy. That’s a biopsy that’s worth it for the patient.

Editor's Note: FoundationOne panel and FoundationOne CDx panel do include NTRK fusions.

Transcript Edited for Clarity
 

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Transcript: 

John L. Marshall, MD:
Let’s shift gears just a little bit. Let’s go fishing. Ever caught an NTRK fusion?

Tanios S. Bekaii-Saab, MD: One.

John L. Marshall, MD: One? You caught 1. Was it a big one or?

Tanios S. Bekaii-Saab, MD: Medium sized.

John L. Marshall, MD: So what we’re talking about here is rare molecular abnormalities. But if you have one, we have medicines now that are very effective. So it changes how we practice.

Tanios S. Bekaii-Saab, MD: It changes how we practice somewhat. I’d say this is not MSI [microsatellite instability]-high and PD-1 [programmed cell death protein 1] inhibitors, but you do see some pretty amazing….

John L. Marshall, MD: I would argue it’s better than. If you have one of these, the response rate is 80%, 90% and with long durable responses.

Tanios S. Bekaii-Saab, MD: For some.

John L. Marshall, MD: Yeah.

Tanios S. Bekaii-Saab, MD: There’s still a question as to whether these responses are going to continue to be solid. With PD-1 inhibitors and MSI, we have 2, 3, 4 years follow-up.

John L. Marshall, MD: But on only 50%, 60% of the people.

Tanios S. Bekaii-Saab, MD: Absolutely. Now I like this. This reinforces the fact that I think that every single patient today with colorectal cancer [CRC], and perhaps all other cancers but at least with colorectal cancer, should get NGS [next-generation sequencing] or a platform that will include these NTRK fusions and other findings. Because as you’ve heard, we have all these good things—MSI, HER2, KRAS, BRAF, NRAS. And I think NTRK should go into that.

John L. Marshall, MD: How do we make sure we know we’re getting this when we order the testing?

Howard S. Hochster, MD, FACP: Right. Well that’s a question, especially if people got Foundation [Medicine] sequencing a little while ago. Those fusions weren’t in there* (see editor's note). So you have to go back.

John L. Marshall, MD: Even the current one doesn’t have all of the NTRKs* (see editor's note).

Howard S. Hochster, MD, FACP: Right. The current FDA approved Foundation panel doesn’t have all of that* (see editor's note). So it is a little bit of a question. It means going back and reading the fine print of what was actually tested for, which we tend to skip. You may need to put on your reading glasses or something like that. But it is worthwhile to make sure that this is tested for, and I think you need to make sure, on your Foundation request, that it is on there.

Tanios S. Bekaii-Saab, MD: Yes. And I think we’re talking about 0.3% to 0 .7% of the patients. But think about it like this. You have 100 patients coming to your clinic. If you don’t test every single one of them, you’re not going to capture that 1. So I think that’s why it’s very important, even more importantly for the lower yield alterations, that patients get access to these tests and eventually to these agents. I’m pretty impressed with the results. I can tell you, in pancreas cancer, you know we’ve seen some data from Mike Pishvaian, MD, PhD, on one of his patients. It’s short of amazing. And these are fantastic responses that we see. This is also a positive predictive biomarker. It really is 1-on-1, unlike a lot of the biomarkers we have in colorectal cancer.

John L. Marshall, MD: I think one of our struggles will be if we don’t have adequate tissue, is something like this, a 1% or under 1% return, worth biopsying? And I think you have to make an individual decision.

Tanios S. Bekaii-Saab, MD: I’d say the answer is, yes. The liquid biopsy component is being refined. It’s still too early. It could be a good alternative in case you don’t have tissue. But right now, I would actually rebiopsy patients. Because it’s not just this NTRK. If you don’t have tissue for NTRK, you probably don’t have tissue for HER2 and others. So I think you should rebiopsy. That’s a biopsy that’s worth it for the patient.

Editor's Note: FoundationOne panel and FoundationOne CDx panel do include NTRK fusions.

Transcript Edited for Clarity
 
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