Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: Final overall survival results of the randomized BRIM-3 study

Paul B. Chapman*, C. Robert, J. Larkin, J. B. Haanen, A. Ribas, D. Hogg, O. Hamid, P. A. Ascierto, A. Testori, P. C. Lorigan, R. Dummer, J. A. Sosman, K. T. Flaherty, I. Chang, S. Coleman, I. Caro, A. Hauschild, G. A. McArthur

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Scopus citations


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 BRAFV600 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/m2 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.

Original languageEnglish (US)
Pages (from-to)2581-2587
Number of pages7
JournalAnnals of Oncology
Issue number10
StatePublished - Oct 2017


  • BRAF mutation
  • Dacarbazine
  • Melanoma
  • Vemurafenib

ASJC Scopus subject areas

  • Hematology
  • Oncology


Dive into the research topics of 'Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: Final overall survival results of the randomized BRIM-3 study'. Together they form a unique fingerprint.

Cite this