We’re bringing it to March because why be controversial only once a year? That and the phase 3 COLUMBUS trial was published yesterday. It randomized 577 patients with advanced (≥IIIB) stage BRAF-mutant melanoma to vemurafenib (BRAF inhibitor) 960 mg BID [1] vs encorafenib (a newer BRAFi with 10x the half-life) 350 mg daily [2] vs combo encorafenib 450 mg daily (yes its more tolerable in combo) + binimetinib (MEK1/2i) 45 mg BID [3]. The primary endpoint of median progression-free survival (PFS) was significantly longer with the new combo therapy (15 months) when compared to both mono encorafenib (10 months) and vemurafenib (7 months). PFS with the combo is also nominally longer than any similar trial evaluating other combo BRAF/MEK inhibition. And did we mention it conferred a lower rate of at least grade 3 toxicity than either monotherapy? TBL: Encorafenib + binimetinib is a new combo treatment for advanced melanoma that’s now positioned to threaten the original BRAF/MEK inhibition teams indigenous to current guidelines.  | Dummer, Lancet Ocol 2018


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