LAUSR

ABSTRACT Introduction: In the treatment of advanced BRAF-mutant melanoma, selective regulation of the MAPK pathway with BRAF and MEK inhibition has emerged as one of the mainstays of therapy. Areas covered: The authors present the current data on encorafenib as a compound, its pharmacokinetic and pharmacodynamics properties. This review includes current data on encorafenib therapy as a single agent as well as in combination with the MEK-inhibitor 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 MEK inhibitors improves response rate, progression-free survival, and overall survival in patients with BRAF-mutant metastatic melanoma compared to prior treatment regimens. Serious adverse events, including the development of cutaneous malignancies, are reported at lower rates with combination therapy, while less severe events such as pyrexia can be more common. Existing data is lacking for a recommendation of triplet therapy, although results from multiple ongoing trials are highly anticipated.