Treatment Sequencing in BRAF+ Metastatic Melanoma

Source: OnClive, July 2019


Ryan J. Sullivan, MD: The only way you ever know if one regimen is better than another is to compare them head to head. In the absence of comparing head to head, you use lots of ancillary data. There’s a lot of extrapolation involved to figure out if one regimen is better than the other. Adverse effects are pretty consistent in terms of comparison. It’s fair to say this drug causes this. Which would you rather have? So I think we can compare across toxicities and say this is the spectrum of adverse effects with vemurafenib/cobimetinib, this is the spectrum of adverse effects of encorafenib/binimetinib. And we can compare them and say maybe we should try this because it could be a little less toxic or we don’t like the fever, or we live in Texas, we’re not going to give you vemurafenib/cobimetinib because of the photosensitivity, but we’ll try one of these other 2 regimens.

I think from an efficacy standpoint, or from a target engagement standpoint, or a potency standpoint, an argument can be made for encorafenib and binimetinib based on 2 pieces of information, maybe 3. The overall survival data from the COLUMBUS study showed that the encorafenib/binimetinib regimen of 450 mg a day of encorafenib and 45 mg BID twice a day of binimetinib was associated with the longest survival we’ve seen in a frontline BRAF-mutated population going on BRAF/MEK inhibitor combination.

That could be a sign of the times, meaning that trial launched after CoBRIM, after COMBI-d, after COMBI-v. And because of that, we had more therapies that were approved and it was more likely that a patient would receive PD-1 [programmed cell death protein 1] inhibitor therapy or combined PD-1, CTLA-4 [cytotoxic T-lymphocyte–associated protein 4] inhibitor therapy after their BRAF-targeted therapy. And so their overall survival might be better because there are better drugs behind it in the patient population that were on COLUMBUS versus those other trials. I don’t know if that’s true, but that’s a reasonable explanation for why the overall survival would have been better.
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