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 BRAFV600-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 BRAFV600-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.

journal_name

Expert Opin Drug Saf

authors

Indini A,Mandalà M

doi

10.1080/14740338.2020.1817376

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1229-1236

issue

10

eissn

1474-0338

issn

1744-764X

journal_volume

19

pub_type

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