Next Steps in Research for BRAF-Mutant NSCLC

Transcript: Bruce E. Johnson, MD: It’s very important to define those patients who are likely to have a long response duration when they’re treated with a BRAF inhibitor and a MEK inhibitor. We think there’s likely to be some genomic or other characteristics within the tumor that we can identify that identifies those patients.

The second thing we need to do in this BRAF population is identify those who are more likely to respond to checkpoint inhibitors versus BRAF and MEK inhibitors. It’s likely that there’s going to be some of each in this group. We know that some of the patients respond for very long periods of time, while others progress in 6 months to a year. That’s No. 1.

No. 2 is that we need more potent and specific drugs. We need better inhibitors of BRAF and better inhibitors of MEK. And lastly, we need to be able to attack different parts of the pathway. One of the things that we can think about is inhibiting the signaling through the RAF family of genes to develop drugs that inhibit not only BRAF but the signaling through ARAF and CRAF; and also, the ability to potentially inhibit not only MEK but also the downstream MAP kinase pathways.

The way I see things developing over the next several years is being able to go after different components of the pathway that BRAF-mutant patients signal through, and expand the number of kinases that we can attack.

No. 2 is being able to know what agents to give after those patients are no longer able to be effectively treated. We want to know whether it’s going to be helpful to give checkpoint inhibition or checkpoint inhibition plus continued tyrosine kinase inhibition, and to convert these people who are surviving for 2 to 4 years to surviving for 5 years or longer.

The ongoing trial that I’d like to call people’s attention to is being able to use encorafenib and binimetinib. The trial is just now opening and beginning to accrue. We’ll be able to compare the antitumor activity of those 2 agents against the already-reported phase II trials of dabrafenib and trametinib.

In addition, we are going to be seeing cohorts of patients treated with vemurafenib and cobimetinib. We’ll see how those particular patients do compared with the others.

And lastly, as the information emerges about combining checkpoint inhibition with BRAF and MEK inhibition, we’ll find out if that’s applicable to the cohort of lung cancer.

Transcript Edited for Clarity