BRAF V600 Mutation and BRAF Kinase Inhibitors in Conjunction With Stereotactic Radiosurgery for Intracranial Melanoma Metastases: A Multicenter Retrospective Study.

BACKGROUND: The BRAF mutation has been identified as a potent target for the treatment of metastatic melanoma and BRAF inhibitors (BRAFi) have demonstrated promising results against melanoma brain metastases (BM). OBJECTIVE: To further investigate the effectiveness of this combined treatment regimen. METHODS: In this multicenter retrospective cohort study, 198 patients with known BRAF mutation status and treated with stereotactic radiosurgery (SRS) between 2011 and 2015 were identified. Kaplan-Meier methodology and multivariate regression analysis was then used to compare survival based on each parameter. RESULTS: The median survival after the diagnosis of BM in patients with BRAF mutation who received BRAFi was increased compared to survival in patients with wild-type BRAF (BRAF wt). In multivariate analysis, the BRAF mutation was an independent, positive prognostic factor with a hazard ratio of 0.59. BRAF mutated Patients who received BRAFi following SRS had improved survival compared to patients who received it before (P < .001) or concurrently (P = .007). PD-1 inhibitors improved survival, with more pronounced effect in patients not carrying the BRAF mutation. Among the patients who were treated with BRAFi, 10.4% developed intracerebral hematoma (ICH), in comparison to 3% of patients who were not treated with BRAFi (P = .03). CONCLUSION: In the setting of widespread use of BRAFi, the presence of a BRAF mutation is an independent predictor of better prognosis in patients with melanoma BM that underwent SRS. The effect of BRAFi is optimal when treatment is initiated at least 1 wk following SRS. BRAFi may increase the frequency of asymptomatic ICH.