Systematic review demonstrates superior survival with combination therapies over monotherapy in BRAF V600-mutant melanoma, highlighting challenges with toxicity and resistance.
Key Points
Synthesize current evidence on the efficacy and safety of targeted therapies, immune checkpoint inhibitors, and combination strategies in BRAF V600-mutant metastatic melanoma.
Systematically reviewed clinical trials assessing BRAF and MEK inhibitors alone and in combination with immune checkpoint inhibitors in BRAF V600-mutant metastatic melanoma.
Evaluated key clinical outcomes including progression-free survival (PFS), overall survival (OS), immune-related adverse events, and molecular mechanisms of drug resistance.
Combination therapies achieved a median progression-free survival of 14.9 to 16.2 months and an overall survival of up to 33.6 months, outperforming BRAF inhibitor monotherapy.
In the COLUMBUS trial, the combination of encorafenib and binimetinib resulted in a median overall survival of 33.6 months compared to 16.9 months with vemurafenib monotherapy.
Treatment durability remains constrained by immune-related adverse events and tumor resistance driven by MAPK pathway reactivation and PI3K-AKT signaling.