An evaluation of encorafenib for the treatment of melanoma

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.

KEYWORDS:

• Targeted therapy
• BRAF
• MEK
• melanoma
• encorafenib
• triplet therapy

Box 1. Drug Summary Box

Table

Article highlights

• Encorafenib is a new FDA approved (in combination with binimetinib- a MEK inhibitor) treatment of BRAF-mutated metastatic melanoma which acts though inhibition of the MAPK pathway.

• Combination of encorafenib with the MEK-inhibiting therapy binimetinib improves patient response, resistance, and adverse events.

• Ongoing investigations of encorafenib/binimetinib in combination with immunotherapy may lead to better outcomes for patients with metastatic melanoma.

Declaration of interest

JS Zager has received research funding from Novartis and has served on the advisory board and serves on the speaker’s bureau of Array Biopharma. Z Eroglu was also on the advisory board of Array Biopharma and Regeneron and has received research funding from Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee received has research grants from Novartis and Pierre Fabre. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.