Key Considerations for Detecting and Targeting BRAF Mutations - Episode 4

Unmet Needs in BRAF+ NSCLC


D. Ross Camidge, MD: In terms of unmet needs, the No. 1 thing is that there are patients who have a BRAF V600E mutation and don’t know it because nobody has tested them. That’s a complete tragedy that is so easy to fix. You should test your patients. It’s part of every guideline. It’s an FDA-approved approach. If you have a non—small cell lung cancer patient, there is no reason not to be testing for BRAF V600E mutations. The second unmet need is, wouldn’t it be great if this regimen was better tolerated? I think that’s challenging, so we just try to manage it as best as we can. Then the third unmet need is that we desperately need next-line targeted therapy, but it has to be informed by the biology of how people develop acquired resistance. We’re always going to look to our melanoma colleagues to figure that out. They have so many more of these patients than we do, but that’s a real unmet need.

At this year’s ASCO [American Society of Clinical Oncology Annual] Meeting, we saw a very small amount of data on using palbociclib, a cell cycle inhibitor, with a response in maybe 1 patient. So I think that’s a work in progress. But generally speaking, at present, if you’re progressing on dabrafenib-trametinib, your next approach is going to be chemotherapy, or immunotherapy, or chemoimmunotherapy, or some known BRAF-directed trial. We don’t yet have a targeted second-line approach.

I think unlike the other driver oncogenes, there is some evidence that the BRAF tends to rise in smokers. They don’t have a somewhat higher tumor mutation burden. Consequently, their response to immunotherapy is the same as that in other lung cancers. It’s running about 23%, 26%. And so I think you’re very free, once you move past the targeted therapy, to consider some kind of immunotherapy approach.

Transcript Edited for Clarity