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).

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.

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.

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.