Expanding Targets in NSCLC - Episode 3

Safety Profiles of BRAF/MEK Inhibitors


Bruce E. Johnson, MD: One of the things that’s unusual about the adverse effects of dabrafenib is it causes fevers. It causes pyrexia, and you have to interrupt the doses, up to a third of the time, for development of fevers. These are not just tiny fevers. These people can get rigors, or chills. It’s important when managing patients that they know how to get in touch with a physician who deals with this commonly, because they will show up in the emergency departments with high fevers and think they’re infected. The first thing you end up doing is interrupting the dabrafenib, or the other BRAF inhibitorsencorafenib and vemurafenib—to allow the fever to subside. If it is persistent after more than 1 or 2 days, you’ll commonly want to give doses of steroids to help control the fever.

The other class of drugs—the MEK inhibitors, which include trametinib, binimetinib, and cobimetinib—commonly cause gastrointestinal [GI] toxicity. They can cause some nausea, some vomiting, and diarrhea. And so, you have to be careful about dose adjusting and be able to effectively manage the patient’s diarrhea, nausea, and vomiting.

The other part is that if they get single-agent BRAF inhibitors, as I mentioned before, the unusual one is they get skin toxicities, meaning they develop malignant lesions. If they’re getting the combination regimen, it’s actually unusual for them to get skin tumors. But we do monitor their skin while they’re getting treated.

The adverse effect profiles have been tested in melanomas. The adverse effect profiles in lung cancer have yet to be compared. As I mentioned before, the only pair that’s been through testing and has been reported on over the last 5 years is the combination of dabrafenib and trametinib. So, it’s difficult to compare.

When you take a look at it in melanoma, if you compare the 3 regimens, there’s not a dramatic difference in the adverse effects between the pairs. It looks like binimetinib and encorafenib may have fewer GI and fever adverse effects.

Transcript Edited for Clarity