Vemurafenib in patients with BRAF(V600) mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study

BACKGROUND: The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAF(V600) mutation–positive metastatic melanoma. We present final OS data from BRIM-3. PATIENTS AND METHODS: Patients were randomly assigned in a 1 : 1 ratio to receive vemurafenib (960 mg twice daily) or dacarbazine (1000 mg/m(2) every 3 weeks). OS and PFS were co-primary end points. OS was assessed in the intention-to-treat population, with and without censoring of data for dacarbazine patients who crossed over to vemurafenib. RESULTS: Between 4 January 2010 and 16 December 2010, a total of 675 patients were randomized to vemurafenib (n = 337) or dacarbazine (n = 338, of whom 84 crossed over to vemurafenib). At the time of database lock (14 August 2015), median OS, censored at crossover, was significantly longer for vemurafenib than for dacarbazine {13.6 months [95% confidence interval (CI) 12.0–15.4] versus 9.7 months [95% CI 7.9–12.8; hazard ratio (HR) 0.81 [95% CI 0.67–0.98]; P = 0.03}, as was median OS without censoring at crossover [13.6 months (95% CI 12.0–15.4) versus 10.3 months (95% CI 9.1–12.8); HR 0.81 (95% CI 0.68–0.96); P = 0.01]. Kaplan–Meier estimates of OS rates for vemurafenib versus dacarbazine were 56% versus 46%, 30% versus 24%, 21% versus 19% and 17% versus 16% at 1, 2, 3 and 4 years, respectively. Overall, 173 of the 338 patients (51%) in the dacarbazine arm and 175 of the 337 (52%) of those in the vemurafenib arm received subsequent anticancer therapies, most commonly ipilimumab. Safety data were consistent with the primary analysis. CONCLUSIONS: Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up. OS curves converged after ≈3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies. CLINICALTRIALS.GOV: NCT01006980.