The discovery and development of binimetinib for the treatment of melanoma.

INTRODUCTION: Binimetinib is an uncompetitive, small-molecule inhibitor of selective mitogen-activated protein kinase (MEK1/2) and was recently approved in 2018 in combination with encorafenib for the treatment of metastatic melanomas. Preclinical and clinical trial data on the drug demonstrate its potent efficacy in cancers, especially melanomas with BRAF and NRAS mutations. AREAS COVERED: The authors review the preclinical as well as clinical Phase 1, 2 and 3 trial data leading to its FDA approval in 2018 for metastatic melanoma. Phase 3 data in combination with encorafenib demonstrated double the PFS (14.9 months) compared to vemurafenib alone (7.3 months) in patients with BRAF-mutated metastatic melanoma. EXPERT OPINION: No longer-term data is available yet to demonstrate any durable complete responses to therapy with binimetinib or improvements in overall survival compared to other FDA-approved therapies including immunotherapy or vemurafenib. Treatment approaches to patients with BRAF-mutated metastatic melanoma should be individualized and binimetinib in combination with encorafenib is a reasonable oral strategy with a reasonably tolerated toxicity profile. The cost of treatment and durability of response should be incorporated into the discussion as part of the overall medical decision-making.