Combined BRAF-Targeted Therapy with Immunotherapy in BRAF-Mutated Advanced Melanoma Patients.

Abstract

To review evidence on the efficacy and safety of combined BRAF-targeted therapy and immune checkpoint inhibitors in patients with BRAF-mutated metastatic melanoma. Programmed death-1 pathway inhibitors administered with BRAF/MEK inhibitors showed promising anti-tumour activity in BRAF-mutated advanced melanoma and were investigated for safety and efficacy in three large international clinical trials. Although, in two out of those three randomized phase III studies, progression-free survival (PFS) did not reach statistical significance, results showed that duration of response (DOR) and overall survival (OS) were improved using combined therapy, sustaining the scientific rationale for its use at least in a subset of metastatic melanomas. However, the frequent occurrence of autoimmunity-induced toxicities should be considered since it is limiting the continuity and the wide application of these regimens. Novel treatment modalities combining targeted therapy with checkpoint inhibitors require further clinical investigation and elucidation of their effect on the immune system and cancer cell modulation.