BACKGROUND & AIM: Brain metastases are frequent in patients with metastatic 
melanoma, indicating poor prognosis. We investigated the BRAF kinase inhibitor 
vemurafenib in patients with advanced melanoma with symptomatic brain 
metastases.
METHODS: This open-label trial assessed vemurafenib (960mg twice a day) in 
patients with BRAF(V600) mutation-positive metastatic melanoma with 
non-resectable, previously treated brain metastases. The primary end-point was 
safety. Secondary end-points included best overall response rate, and 
progression-free and overall survival.
RESULTS: Twenty-four patients received vemurafenib for a median treatment 
duration of 3.8 (0.1-11.3) months. The majority of discontinuations were due to 
disease progression (n=22). Twenty-three of 24 patients reported at least one 
adverse event (AE). Grade 3 AEs were reported in four (17%; 95% confidence 
interval [CI], 4.7-37.4%) patients and included cutaneous squamous cell 
carcinoma in four patients. Median progression-free survival was 3.9 (95% CI, 
3.0-5.5) months, and median survival was 5.3 (95% CI, 3.9-6.6) months. An 
overall partial response (PR) at both intracranial and extracranial sites was 
achieved in 10 of 24 (42%; 95% CI, 22.1-63.4) evaluable patients, with stable 
disease in nine (38%; 95% CI, 18.8-59.4) patients. Of 19 patients with 
measurable intracranial disease, seven (37%) achieved >30% intracranial tumour 
regression, and three (16%; 95% CI, 3.4-39.6%) achieved a confirmed PR. Other 
signs of improvement included reduced need for corticosteroids and enhanced 
performance status.
CONCLUSIONS: Vemurafenib can be safely used in patients with advanced 
symptomatic melanoma that has metastasised to the brain and can result in 
meaningful tumour regression.