Expanding Targets in NSCLC - Episode 12

Treating METex14 Mutations in NSCLC

Transcript: Edward B. Garon, MD: My referring physicians often ask, “What do you do when you encounter a MET exon 14 skipping mutation?” For me, the answer is easy. We’ve been involved in clinical trials of capmatinib and we’ve tried to get them on those trials. My first question to them is, are they interested in referring patients for clinical trials? Capmatinib is the study we had, but there are other agents that have certainly been under investigation. Across town, there’s a study looking at tepotinib, which is also clearly a very active agent. Crizotinib also has been evaluated in clinical trials.

Crizotinib is the 1 that is probably most frequently used by practitioners in the community now if they don’t have a clinical trial to refer to. It is an available MET inhibitor. Again, it was originally developed as a MET inhibitor. And so that is a drug that is available. The other drug that I have sometimes seen people use in this setting is cabozantinib. It also is clearly an agent that is effective against MET and has been used. Again, both crizotinib and cabozantinib would be used off-label for this. Neither has an approval in this population, but that’s what I have generally seen practitioners do if they don’t have access to a clinical trial.

Alexander Spira, MD, PhD, FACP: Historically, most patients who had exon 14 skipping mutations in the MET gene probably were not even treated with a targeted therapy. They were probably just treated with chemotherapy. There have been off-label uses for a drug called crizotinib, mainly, which has been shown to be pretty potent in terms of activity against exon 14 skipping.

The unmet needs for this patient population are several-fold. No. 1 is an FDA approved drug. Once a drug is FDA-approved, it’s easier to get and there’s more general understanding. Even understanding the role of the MET oncogene and testing for it, it was not that common. So I’m sure there are many patients who had this who were missed as well.

Crizotinib was originally developed as a MET inhibitor a long time ago. It is not fully specific for MET. It’s what we call a little more dirty. So not as active, although there is activity there that leads to the desire to develop drugs that are much more specific for MET, which will hopefully be more potent and have fewer adverse effects.

Transcript Edited for Clarity