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

P 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

Research output: Contribution to journalArticle

Abstract

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.

ClinicalTrials.gov: NCT01006980.

Original languageEnglish
Pages (from-to)2581-2587
Number of pages7
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

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Chapman, P. B., Robert, C., Larkin, J., Haanen, J. B., Ribas, A., Hogg, D., Hamid, O., Ascierto, P. A., Testori, A., Lorigan, P. C., Dummer, R., Sosman, J. A., Flaherty, K. T., Chang, I., Coleman, S., Caro, I., Hauschild, A., & McArthur, G. A. (2017). Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study. Annals of oncology : official journal of the European Society for Medical Oncology, 28(10), 2581-2587. https://doi.org/10.1093/annonc/mdx339