Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma

作者: James Larkin , Paolo A. Ascierto , Brigitte Dréno , Victoria Atkinson , Gabriella Liszkay

DOI: 10.1056/NEJMOA1408868

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摘要: BACKGROUND The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset resistance observed inhibitors alone. This randomized phase 3 study evaluated combination inhibitor vemurafenib cobimetinib. METHODS We randomly assigned 495 previously untreated unresectable locally advanced metastatic V600 mutation–positive receive cobimetinib (combination group) placebo (control group). primary end point was investigator-assessed progression-free survival. RESULTS median survival 9.9 months group 6.2 control (hazard ratio for death disease progression, 0.51; 95% confidence interval [CI], 0.39 0.68; P<0.001). rate complete partial response 68%, as compared 45% (P<0.001), including rates 10% 4% group. Progression-free assessed independent review similar Interim analyses overall showed 9-month 81% (95% CI, 75 87) 73% 65 80) Vemurafenib associated a nonsignificantly higher incidence adverse events grade higher, (65% vs. 59%), there no significant difference study-drug discontinuation. number secondary cutaneous cancers decreased therapy. CONCLUSIONS addition improvement among V600–mutated melanoma, at cost some increase toxicity. (Funded F. Hoffmann– La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.)

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