METex14-Mutated NSCLC: Next Steps in Research

Transcript:Alexander Spira, MD, PhD, FACP: Over the last couple of years, we’ve had many, many more rare therapies, especially for lung cancer, which has really led the field. The approval of a MET inhibitor is just going to expand on that. We have more drugs for relatively rare diagnoses. It’s to be a big leap forward, or a middle leap for a very small percentage of patients. But there are a few of these now, so it’s going to require more testing, more tissue stewardship, and the ability of oncologists to test for and understand these rare mutations.

For a general oncologist who doesn’t see a lot of lung cancer patients—it may be a year, or 2 years, or even longer before they see 1—it’s going to be very important to get that message across, so patients can be not only tested for it but, of course, given the drugs that work super well.

Edward B. Garon, MD: I think that, again, it is very exciting—the idea of having another sizable population of patients with lung cancer who would have an available and tolerable targeted agent that they could use to induce responses, have nice durations of response, and presumably allow them to live better and longer.

Alexander Spira, MD, PhD, FACP: It’s going to be very exciting once these drugs get approved. We all assume that they will. The next questions will be: Can you use them in the first-line setting, and should you use them in the first line? Is it going to be better to give chemotherapy and checkpoint inhibitors, or is it better to give this? Obviously, then there are other questions. Should they be given with chemotherapy? How do they interact with other drugs? Those studies take a lot more time. And obviously, in a very small patient population, those studies are tough to do.

Using the example of ALK and EGFR, it took years before we made that leap into the first-line setting, especially with the ALK story. There are going to be a lot of questions. And then, of course, the next question is, the median duration of response is not forever. It’s usually in the order of 8 to 12 months. What do we do after that? We hope that there are going to be second-line and third-line drugs down the road, but those obviously need to be not only developed but then tested in clinical studies.

Edward B. Garon, MD: I think very little is known, to date, about acquired resistance from MET inhibitors; and I think that’s what is to be expected in a setting where we have very few patients who are treated to date. I think this will be an area of active investigation and will be important.

We do know that there is an impressive duration of response, but it is not in excess of a year. We are going to want to know what the reasons are for why the drug stops working, so ideally, we can devise even better therapies for this group of patients who have MET exon 14 skipping mutations.

As you know, there are registration trials for multiple agents at this point in this class. Dr Heist, for instance, does have a trial of capmatinib in patients who have previously received a MET-directed therapy. I think that is going to be an important area of research. I think particularly as more and more people are getting this class of drugs, approaches to combat resistance are going to be important in just assessing what happens at the time of resistance.

Transcript Edited for Clarity