PURPOSE: Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase. 
Our multicenter, single-arm, phase II study assessed the safety and clinical 
activity of dabrafenib in BRAF(V600E/K) mutation-positive metastatic melanoma 
(mut(+) MM).
PATIENTS AND METHODS: Histologically confirmed patients with stage IV 
BRAF(V600E/K) mut(+) MM received oral dabrafenib 150 mg twice daily until 
disease progression, death, or unacceptable adverse events (AEs). The primary 
end point was investigator-assessed overall response rate in BRAF(V600E) mut(+) 
MM patients. Secondary end points included progression-free survival (PFS) and 
overall survival (OS). Exploratory objectives included the comparison of BRAF 
mutation status between tumor-specific circulating cell-free DNA (cfDNA) and 
tumor tissue, and the evaluation of cfDNA as a predictor of clinical outcome.
RESULTS: Seventy-six patients with BRAF(V600E) and 16 patients with BRAF(V600K) 
mut(+) MM were enrolled onto the study. In the BRAF(V600E) group, 45 patients 
(59%) had a confirmed response (95% CI, 48.2 to 70.3), including five patients 
(7%) with complete responses. Two patients (13%) with BRAF(V600K) mut(+) MM had 
a confirmed partial response (95% CI, 0 to 28.7). In the BRAF(V600E) and 
BRAF(V600K) groups, median PFS was 6.3 months and 4.5 months, and median OS was 
13.1 months and 12.9 months, respectively. The most common AEs were arthralgia 
(33%), hyperkeratosis (27%), and pyrexia (24%). Overall, 25 patients (27%) 
experienced a serious AE and nine patients (10%) had squamous cell carcinoma. 
Baseline cfDNA levels predicted response rate and PFS in BRAF(V600E) mut(+) MM 
patients.
CONCLUSION: Dabrafenib was well tolerated and clinically active in patients with 
BRAF(V600E/K) mut(+) MM. cfDNA may be a useful prognostic and response marker in 
future studies.