(CHICAGO, IL) – Vemurafenib improved overall survival (OS) in patients with BRAF600E-mutated metastatic melanoma, results of a Phase 3 study presented at the 2012 American Society of Clinical Oncology Annual Meeting has found.

The presentation provided updated OS results for the randomized, open-label, multicenter BRIM-3 trial that compared the BRAF inhibitor vemurafenib with dacarbazine in previously untreated patients. The study was headed by Paul B. Chapman, MD, a physician-scientist of Memorial Sloan-Kettering Cancer Center, New York, NY.

The patient population (n=675) was randomized to 960mg twice-daily oral vemurafenib (n=337) or 1000mg/m2 intravenous dacarbazine every three weeks (n=338). They were then monitored to the co-primary endpoints of OS and progression-free survival (PFS).

At the February 1, 2012 data cut-off, median follow-up was 12.5 months for vemurafenib and 9.5 months for dacarbazine. In patients not censored at crossover, median OS was 13.6 months for vemurafenib vs. 10.3 months for dacarbazine (HR 0.76; P<0.01 post-hoc). In those censored at crossover, OS was 13.6 months for vemurafenib and 9.7 months for dacarbazine (HR 0.76; P<0.001 post-hoc).

A total of 44% of patients in the dacarbazine arm and 36% in the vemurafenib arm received any subsequent anticancer therapy; of these, 22% in the dacarbazine arm and 18% in the vemurafenib arm received ipilimumab and 83 patients (25%) in the dacarbazine arm crossed over to vemurafenib.

In the patients censored at crossover, vemurafenib also improved PFS (median 6.9 months vs. 1.6 months for dacarbazine; HR 0.38; P<0.001 log-rank post-hoc). OS and PFS by baseline characteristic — including age, sex, ECOG status, disease stage, and LDH—favored vemurafenib vs dacarbazine; for OS, the 95% confidence interval crossed for disease stage IIIc, M1a and M1b disease.

Objective response rate was 57% for the vemurafenib arm (5.6% complete responses and 51.3% partial responses) and 8.6% for dacarbazine (1.2% complete responses and 7.4% partial responses).

Selected adverse events that occurred more frequently in the vemurafenib group included cutaneous squamous cell carcinoma, keratoacanthoma, and skin papilloma; 8 patients in the vemurafenib group reported new primary melanomas.

“Vemurafenib continues to be associated with improved efficacy compared with dacarbazine,” Dr. Chapman concluded.

Abstract