BRAF/MEK Inhibitors in Metastatic Melanoma

Source: OncLive, August 2019

Jeffrey S. Weber, MD, PhD: We’re talking about BRAF/MEK, but what about the new kids on the block? I mean, encorafenib and binimetinib are relatively recently developed drugs. Jason, what can you tell us about encorafenib and binimetinib? Different mode of action, different drugs, different adverse-effect profile.

Jason J. Luke, MD, FACP: Encorafenib and binimetinib are the third BRAF/MEK combination to gain regulatory approval. I think it’s interesting to observe that the development of these drugs was informed by the development of the previous generations of BRAF and MEK inhibitors. Specifically, what I mean by that is that it’s clear from the previous studies that adding the MEK inhibitor decreased the BRAF inhibitor toxicity. We don’t have time to dive into all that, but we know that from other studies.

In the study of encorafenib and binimetinib, in phase I, they pushed the dose of the encorafenib up a little higher than the 1-for-1 dose that you would see with the currently available BRAF inhibitors. That’s very interesting, because we have this hypothesis that if you really suppress BRAF in its downstream signaling, you could get a better benefit.

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