Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma

“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 BRAFV600E/K mutation–positive metastatic melanoma (mut+ MM). Patients and Methods: Histologically confirmed patients with stage IV BRAFV600E/Kmut+ 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 BRAFV600E 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…Conclusion: Dabrafenib was well tolerated and clinically active in patients withBRAFV600E/K mut+ MM. cfDNA may be a useful prognostic and response marker in future studies.”