Vemurafenib, a selective BRAF inhibitor, has recently shown an improved overall survival (OS) in metastatic
melanoma with V600E mutation in phase 2 and 3 trials. Patients with BRAF V600E metastatic
melanoma received
vemurafenib orally, in the French temporary authorization for use program from April 2011 to April 2012. We analysed the clinical benefit and safety of
vemurafenib. Secondary analyses included the impact of
brain metastases on median OS and progression-free survival (PFS). Fifty patients were enrolled, of whom 20% had stage IIIC and 80% stage IV disease. The majority were men (58%), with a median age of 58 years (51-69). Forty-three patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 (86%). Twenty patients had
brain metastases (40%). Overall response rate was 53%. Complete response was achieved in five patients (10%), partial response in 21 patients (43%) and stable disease in seven patients (14%). Median OS was 7.5 months (95% confidence interval 5.6-12.7) and PFS was 3.6 months (95% confidence interval 2.9-5.9). Patients with brain
metastasis had a response rate of 50% (nine partial response, one complete response), and median OS and PFS were, respectively, 4.3 and 3.1 months. Common adverse events were
fatigue,
arthralgia and cutaneous side effects. Sixteen per cent developed
squamous cell carcinoma. Grade 3/4 was observed in 11 patients (22%). Six per cent required temporary discontinuation and/or
dose reduction because of toxic effects. This study confirms the considerable clinical benefit of
vemurafenib for patients with brain
metastasis, with manageable toxicity.