A costly revolution for a subgroup of patients with metastatic melanoma

Background Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in phase I and II studies in patients with BRAF (V600)-mutated metastatic melanoma. Hauschild et al. aimed to assess the efficacy of dabrafenib in a phase III trial of patients with BRAF (V600)-mutated metastatic melanoma. Methods Patients were enrolled into a phase III trial between December 2010 and September 2011. This report is based on the cut-off date of 19 December 2011. Patients with previously untreated stage IV or unresectable stage III BRAF (V600)-mutated melanoma were randomly assigned (3: 1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg m(-2) intravenously every 3 weeks). Patients were stratified according to American Joint Committee on Cancer stage. The primary endpoint w Findings Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients). Median PFS was 5 1 months for dabrafenib and 2 7 months for dacarbazine, with a hazard ratio of 0.30 (95% confidence interval 0.18-0.51, P < 0 0001). At cut-off, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomized treatment. Treatment-related adverse events (grade 2 or higher) occurred in 100 (53%) of the 1 Interpretation Dabrafenib significantly improved PFS compared with dacarbazine.