BACKGROUND: Phase 1 and 2 clinical trials of the BRAF kinase inhibitor 
vemurafenib (PLX4032) have shown response rates of more than 50% in patients 
with metastatic melanoma with the BRAF V600E mutation.
METHODS: We conducted a phase 3 randomized clinical trial comparing vemurafenib 
with dacarbazine in 675 patients with previously untreated, metastatic melanoma 
with the BRAF V600E mutation. Patients were randomly assigned to receive either 
vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter 
of body-surface area intravenously every 3 weeks). Coprimary end points were 
rates of overall and progression-free survival. Secondary end points included 
the response rate, response duration, and safety. A final analysis was planned 
after 196 deaths and an interim analysis after 98 deaths.
RESULTS: At 6 months, overall survival was 84% (95% confidence interval [CI], 78 
to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine 
group. In the interim analysis for overall survival and final analysis for 
progression-free survival, vemurafenib was associated with a relative reduction 
of 63% in the risk of death and of 74% in the risk of either death or disease 
progression, as compared with dacarbazine (P<0.001 for both comparisons). After 
review of the interim analysis by an independent data and safety monitoring 
board, crossover from dacarbazine to vemurafenib was recommended. Response rates 
were 48% for vemurafenib and 5% for dacarbazine. Common adverse events 
associated with vemurafenib were arthralgia, rash, fatigue, alopecia, 
keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and 
diarrhea; 38% of patients required dose modification because of toxic effects.
CONCLUSIONS: Vemurafenib produced improved rates of overall and progression-free 
survival in patients with previously untreated melanoma with the BRAF V600E 
mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, 
NCT01006980.).