The combination of encorafenib and binimetinib for the treatment of patients with BRAF-mutated advanced, unresectable, or metastatic melanoma: an update

Abstract

ABSTRACT Introduction: In the treatment of advanced BRAF-mutated melanoma, selective regulation of the MAPK pathway with BRAF and MEK inhibition has emerged as one of the mainstays of therapy. Areas covered: Introduction of MAPK pathway. Current data on BRAF inhibition from phase I, II, and III trials in the setting of unresectable disease. Current data on encorafenib and binietinib, their chemistry, pharmacokinetic, and pharmacodynamic properties. Discussion on use of encorafenib therapy as a single agent as well as in combination with binimetinib and other systemic therapies. Expert opinion: BRAF inhibition with encorafenib exhibits substantial antitumor activity with less paradoxical MAPK pathway activation leading to treatment resistance. Combination therapy with binimetinib improves response rate, progression-free survival, and overall survival in patients with BRAF-mutated unresectable, metastatic melanoma. Serious adverse events, including development of cutaneous malignancies, are reported at lower rates with combination therapy, while less severe events such as pyrexia can be more common.