Modern systemic therapy for patients with BRAF-mutant melanoma and brain metastases: a scoping review

Abstract

Background: brain metastases in patients with melanoma represent one of the most unfavorable clinical scenarios. In patients with a BRAF gene mutation, several treatment tactics may be considered. Aim: to assess the potential of contemporary treatment modalities for patients with BRAF-mutant melanoma and brain metastases, as well as to identify metrics used to evaluate their efficacy. Materials and Methods: a scoping review methodology was used for source selection. The search was performed in PubMed, eLIBRARY, and reference lists. Of 225 publications identified, 29 studies were included in this review to assess treatment efficacy parameters. Factors affecting treatment outcomes in multivariable models were also reviewed. Results: a pooled efficacy assessment of all treatment modalities revealed high heterogeneity among the included studies (p<0.001). The mean objective response rate (ORR) with targeted therapy (TT) was 52% (95% confidence interval [CI] 41–64%), the pooled median time to progression (TTP) was 6.94 months (95% CI 5.34–8.54), and the pooled median overall survival (OS) was 12.55 months (95% CI 10.74– 14.37). For immunotherapy (IT), the ORR reported in the only available study was 15% (95% CI 0–33.4%); the pooled median TTP was 10.37 months (95% CI 1.19–18.83), and the pooled median OS was 15.77 months (95% CI 11.55–19.99). The literature analysis indicates high efficacy of contemporary immunotherapy and targeted therapy approaches in patients with BRAF- mutant melanoma and central nervous system metastases. Targeted therapy is the most extensively studied treatment modality and appears to offer particular benefits in patients with symptomatic metastases and in second and subsequent therapy lines. The combination of encorafenib and binimetinib demonstrated the highest efficacy rates. Conclusion: given the considerable number of factors that may potentially influence the efficacy of both targeted therapy and immunotherapy, randomized controlled trials are needed to determine the optimal sequencing of contemporary systemic treatment modalities in patients with BRAF-mutant melanoma and brain metastases. KEYWORDS: melanoma, brain metastases, BRAF-mutation, immunotherapy, targeted therapy, objective response rate, overall survival, time to progression, encorafenib, binimetinib. FOR CITATION: Novik A.V. Modern systemic therapy for patients with BRAF-mutant melanoma and brain metastases: a scoping review. Russian Medical Inquiry. 2026;10(7):500–508 (in Russ.). DOI: 10.32364/2587-6821-2026-10-7-7