INTRODUCTION: Approximately 50% of patients with cutaneous melanoma have an 
activating mutation in BRAF kinase, leading to constitutive activation of the 
mitogen-activated protein kinase pathway and unregulated cell growth. Selective 
inhibitors of the mutated BRAF kinase produce response rates of approximately 
50% with median progression-free survival of 6 - 7 months. BRAF-blocking 
therapies work rapidly, with responses seen within 2 weeks after therapy 
initiation, and they are associated with generally mild toxicities. The BRAF 
inhibitor dabrafenib recently was approved for use in patients with BRAF 
V600-mutated metastatic melanoma.
AREAS COVERED: This article discusses the mechanisms of action and 
pharmacokinetic and pharmacodynamic changes as well as clinical efficacy and 
safety of dabrafenib for treatment of patients with advanced melanoma including 
unresectable stage IIIc and stage IV patients who harbor a BRAF V600 mutation. 
Clinical trial data are reviewed, and efficacy of dabrafenib in patients with 
brain metastases and in combination with the MEK inhibitor trametinib is 
discussed.
EXPERT OPINION: Despite rapid and significant tumor reduction in a majority of 
patients with BRAF-mutant metastatic melanoma who are treated with dabrafenib, 
this drug's use as a single agent is limited because of its relatively short 
duration of response. Various combinations with drug(s) inhibiting other target 
kinases and/or with immunomodulating agent(s) will likely be the standard in the 
near future.