A systematic review of contemporary therapeutic strategies for BRAF V600 mutant melanoma

Melanoma is diagnosed in 40–50% of patients exhibiting the BRAF V600 mutation, which has affected the cancer treatment. This mutation causes unresponsive tumor growth and, for that reason, BRAF and MEK inhibitors target this particular mutational landscape. Thus, new achievements include the possibility of using targeted therapies in combination with immune checkpoint inhibitors to enhance clinical efficacy. In all trials included, combination therapies showed median PFS of 14.9 to 16.2 months and OS of up to 33.6 months, both of which are superior to BRAF inhibitor monotherapy. This study synthesized current data on targeted agents, immune checkpoint inhibitors, and combinations in BRAF V600-mutant metastatic melanoma. BRAF/MEK in combination with checkpoint inhibitors shows significantly better PFS and OS than monotherapy. Many prominent studies have been conducted, including the COLUMBUS trials (median OS with Encorafenib + Binimetinib = 33.6 months vs. vemurafenib = 16.9 months), which have demonstrated enhanced results with these methods. Nevertheless, more instances of irAEs remain a problem for researchers. Although these advantages have been achieved, the resistance that results from MAPK pathway reactivation and PI3K-AKT signaling remains a limitation to long-term therapeutic durability. Combination treatment approaches have the best clinical outcome in BRAF V600 mutant melanoma, as opposed to monotherapy, but toxicity is a major limitation. Future clinical studies should focus on optimizing treatment sequencing, minimizing host- and targeted-therapy-related toxicities, and implementing other strategies to overcome resistance. New biomarker-based surveillance plans can also improve on treatment sequencing and resistance management in the future.