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Dabrafenib is a potent BRAF inhibitor, which showed intracranial tumor activity. The purpose of our retrospective analysis was to evaluate the efficacy of dabrafenib for patients with melanoma brain metastasis (BM). We studied 30 BRAF mutant melanoma patients with BM, who received dabrafenib after local control of the brain between 2014 and 2017. Eastern Cooperative Oncology Group Performance Status (ECOG) was 0–2. The control arm consisted of 204 melanoma patients from our institutional melanoma database with BM and ECOG 0–2 treated with local therapies and/or chemotherapy, between 2003 and 2015. We found the intracranial disease control rate (DCR) was 83% including four (13%) complete remissions (CR), nine (30%) partial remissions (PR) and twelve (40%) stable diseases (SD) in contrast to five (17%) progressive diseases (PD). With a median follow-up of 14 months, median progression-free survival (PFS) and overall survival (OS) were 5.5 months, and 8.8 months, respectively. If calculated from BM onset, the OS turned to be 11.8 months on the dabrafenib arm, while it was only 6.0 months in the control arm (HR = 0.45,
p
= 0.0014). Higher risk of progression was observed with increasing ECOG (HR =4.06,
p
= 0.00027) and if more than 2 extracranial organs were involved (HR = 3.4,
p
= 0.0077). Elevated lactate dehydrogenase (LDH) was non-significantly associated with worse clinical outcome. Remarkable intracranial activity of dabrafenib in real practice was confirmed by our analysis.