Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

Abstract (PubMed)

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 (PFS). RESULTS: At 6 months, overall survival was 84% in the vemurafenib group and 64% 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 (HR 0.37; 95% CI 0.26-0.55) and of 74% in the risk of disease progression (HR 0.26; 95% CI 0.20-0.33) (P<0.001). Cutaneous events, arthralgia, fatigue, and photosensitivity were the most common adverse events. 38% required dose modification. Cutaneous squamous-cell carcinoma/keratoacanthoma 18%. CONCLUSIONS: Vemurafenib produced improved rates of overall and progression-free survival vs dacarbazine in patients with metastatic melanoma with BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov NCT01006980.)