Safety and efficacy evaluation of encorafenib plus binimetinib for the treatment of advanced BRAF-mutant melanoma patients

ABSTRACT

Introduction

Approximately 40–50% of patients with cutaneous melanoma harbor point mutations in BRAF. BRAF and MEK inhibitors in combination are now a standard therapy for advanced BRAF ^V600-mutated melanoma. Nevertheless, survival rates with the combination are limited, highlighting the need for further therapeutic improvement and strategies to overcome primary and acquired resistance.

Areas covered

Encorafenib, a highly selective BRAF inhibitor, was developed in combination with binimetinib, a potent, selective allosteric MEK1/2 inhibitor, to improve efficacy and tolerability over other approved combo-targeted therapies. This novel combination shows peculiar pharmacodynamic properties which translate in a higher on-target potency and paradox index. Consistent survival improvements for encorafenib and binimetinib in BRAF ^V600-mutated melanoma have been confirmed in clinical trials, with over 4 years of median follow up.

Expert opinion

the favorable survival results and the attractive toxicity profile suggest that encorafenib and binimetinib combination is an intriguing standard option when targeted therapies are considered as first line treatment in BRAF mutated melanoma patients. In the near future, results from ongoing clinical trials will provide information on the use of this novel combination in specific situation, including as adjuvant treatment or as a combination strategy.

KEYWORDS:

• Encorafenib
• binimetinib
• melanoma
• braf
• mek
• targeted therapy

Drug summary box

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Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Pierre Fabre and Pfizer provided a scientific accuracy review at the request of the journal editor.

Declaration of interest

Over the last 2 years, M Mandalà has received consulting fees from Bristol-Myers Squibb and Pierre Fabre Pharmaceuticals, advisory board fees from Merck, Pierre Fabre Pharmaceuticals and Sanofi Aventis, and grant support and advisory board fees 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.