Department of Pharmacology, University of Michigan , Ann Arbor, MI, USA.
Department of Surgery, University of Michigan , Ann Arbor, MI, USA.
Expert Opin Drug Discov. 2020 Jul;15(7):745-754. doi: 10.1080/17460441.2020.1746265. Epub 2020 Apr 4.
Binimetinib is an uncompetitive, small-molecule inhibitor of selective mitogen-activated protein kinase (1/2) 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 and mutations.
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.
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.
Binimetinib 是一种非竞争性、小分子选择性丝裂原活化蛋白激酶（1/2）抑制剂，于 2018 年被批准与 encorafenib 联合用于治疗转移性黑色素瘤。该药的临床前和临床试验数据表明其在癌症，特别是具有 和 突变的黑色素瘤中具有强大的疗效。
作者回顾了导致该药于 2018 年获得 FDA 批准用于转移性黑色素瘤的临床前和临床 1、2 和 3 期试验数据。与单独使用 vemurafenib（7.3 个月）相比，联合 encorafenib 的 3 期数据显示，BRAF 突变转移性黑色素瘤患者的无进展生存期（PFS）增加了一倍（14.9 个月）。
目前尚无更长时间的数据可证明与其他 FDA 批准的治疗方法（包括免疫疗法或 vemurafenib）相比，binimetinib 或改善总体生存率有任何持久的完全缓解。对于 BRAF 突变转移性黑色素瘤患者的治疗方法应个体化，binimetinib 联合 encorafenib 是一种合理的口服治疗策略，其毒性谱可耐受。在总体医疗决策中，应将治疗费用和缓解持续时间纳入讨论。
