TRK Inhibitors in Lung and GI Cancers - Episode 6

Genomic Testing for NTRK Fusions in Lung and GI Cancers

, , , , ,

John L. Marshall, MD: Dr Patel, Jyoti, tell me, for general oncologists, what do you want to do in lung cancer patients?

Jyoti D. Patel, MD: I think you really need multidisciplinary buy-in. You need good conversation with the pathologists. They need to understand the clinical relevance of these oncogenic drivers and why we prioritize them. One reason so many of us medical oncologists have gravitated toward blood-based testing is we control it. We can send a nurse to someone’s house to get the blood. The results come straight to us. We can look at the time flow and make it happen according to our needs.

With pathology it can be more cumbersome. Some institutions, such as ours, have been able to do reflex testing for all adenocarcinomas at diagnosis or all nonsquamous cancers at diagnosis and then special one-offs. That takes shared effort and decisions about what you can do in house and what needs to be sent out.

Initially there’s a new diagnosis at tumor board, and what does the general oncologist do? Talk to the pathologist. How soon can you get this tissue? This is because you may ask for a send-out lab, but it may sit in the lab—particularly during these crazy times—for a week before it even gets sent to the outside laboratory. Some type of workflow within your institution that makes sure these happen quickly is absolutely essential.

John L. Marshall, MD: You work at Northwestern University, right? Are the pathologists giving you trouble there?

Jyoti D. Patel, MD: No, it’s been great. We’ve been able to tie in a shared model of reflex testing, and they help us control tissue. We have shown, along with multiple others, that if you have that, it shortens the time to treatment initiation to getting results.

John L. Marshall, MD: Yeah, Luis?

Luis E. Raez, MD: I have a comment to complement what Jyoti is saying. You’re talking about our institutions where we have certain authority to ask the pathologists that can be your friend, “Please send the tissue.” But remember, all of us are at referral centers. A lot of the patients that come to our centers, because they’re very large centers, come from a hospital from some city around you. You don’t have any authority when you request to have the tissue delivered where you want to send the test.

That’s the main problem—the referral hospital wants to send the tissue 3 weeks from now. There is no way around, to call them and ask a favor to do it. That’s a major problem that we have, and that’s why in plasma it’s very helpful sometimes because we can send it right away.

John L. Marshall, MD: Go ahead, Mark. I’m sorry.

Mark A. Socinski, MD: I agree with Luis. That’s part of the reason why there’s a particular vendor that will go directly to the source of where the tissue is. I call them the golden retriever of molecular testing vendors. You just throw the tennis ball to that hospital, they go get the tennis ball, and it just takes us out of the loop. They still have trouble getting it quickly, but at least they take us out of the loop.

John L. Marshall, MD: Yeah, there was an interesting time when I sent a test on a patient, and he was a physician. It was his own institution where his tissue was, and his pathologist wouldn’t release the tissue. I had to call the pathologist, and they sent the block to me. We don’t want to get in the weeds of that. It really is a barrier to getting access and getting it sent out.

Tony, let me ask you a hard question about this, because you love pancreatic cancer—or hate it, I should say. It’s not uncommon for us to have a very small amount, like the lung cancer folks get. What’s it worth doing to get tissue enough to send for broad testing? Do you go for a repeat biopsy? Do you try to use circulating markers? Tony, what are you doing in pancreatic cancer when you don’t have enough tissue?

Tanios S. Bekaii-Saab, MD, FACP: This is a very particular challenge in this type of cancer. The problem is, the liquid piece is even more challenging with pancreatic cancer than a lot of cancers. These tend to be low-volume types of cancer, and they shed very low DNA. You do find them, but they shed very low DNA. The return is actually not as powerful. That said, we’ve used it, and many times we find what you would expect—no alterations because you can’t find the DNA.

I actually tried everything possible to have a tissue biopsy on these patients. First, we trained our gastroenterologists. We said most of these patients may come with the tissue already, or whatever tissue they’ve got. But for our patients, even in the locally advanced where you typically have endoscopic ultrasound, you have very low tissue. We actually have trained them to try to get a larger core, like a 19-gauge needle rather than a 22-gauge or a 25-gauge—whatever they use—to give us enough to be able to run a test.

For those with liver lesions—again, most of those patients with metastatic disease will have liver lesions if they just had an endoscopic ultrasound with scant tissue—I’m doing a biopsy on the liver. I think it’s justifiable. One may argue with pancreatic cancer that most of these patients will have nothing. But for the 10% to 15% that will have something, it could be quite significant. It could be an NTRK fusion, it could be MSI [microsatellite] high—those are 0.5% to 1.0%. But you know what? We find them, and they have remarkable responses.

We’re finding HER2 [human epidermal growth factor 2], we’re finding BRAF and now NRG fusions, which certainly in the lung world as well are becoming relevant in our trials, as well as RAS B12 and then BRCA. So these are little pieces—a needle here, a needle there. Even if you test germline in the negative, you still have a 50/50 chance if they have a BRCA mutation that the BRCA will be somatic, not germline, and those actually respond equally well to the PARP inhibitors.

If you put all this together, there’s about 10% to 15%, so it’s not a majority. But for a disease that does incredibly bad, these are important because they help us and direct us in terms of treatment. I’m very aggressive trying to get a biopsy on those patients in whichever way I can.

John L. Marshall, MD: It comes back to Jyoti’s comment about this team multidisciplinary approach. I bet every one of us would nod that we have a deal with interventional radiology. If they’re down there for a tissue, not just for a diagnosis but for profiling, it’s really changed the SOP [standard operating procedure] in many ways, referrals for tissue acquisition. I think it’s just critical for us all to do that.

Transcript edited for clarity.