Department of Cutaneous Oncology, Moffitt Cancer Center , Tampa, FL, USA.
School of Pharmacy, Lake Erie College of Osteopathic Medicine , Bradenton, FL, USA.
Expert Opin Drug Discov. 2020 Dec;15(12):1373-1380. doi: 10.1080/17460441.2020.1795124. Epub 2020 Jul 28.
Nearly 50% of patients with metastatic melanoma harbor a BRAFV600-mutation, which can be targeted with the use of BRAF and MEK inhibitors, either in the front-line or treatment-refractory setting. Encorafenib is the newest BRAF-inhibitor to have received FDA-approval in combination with the MEK inhibitor binimetinib.
The authors provide an overview of the preclinical development and the clinical trials that led to the use of encorafenib in BRAFV600-mutant melanoma. They also give discussion on its current use in clinical practice, providing their expert perspectives on the subject.
Preclinical research has provided strong rationale for upgrading encorafenib investigation into clinical development/testing. However, there is not yet enough data to determine where encorafenib may fit in comparison to other drugs in the same class, and ongoing trials will further define its role in the treatment of melanoma. Of note, there are ongoing studies that further explore the role of encorafenib + binimetinib such as in combination regimens with immunotherapy drugs, and in brain metastases.
近 50%的转移性黑色素瘤患者携带 BRAFV600 突变，可使用 BRAF 和 MEK 抑制剂进行靶向治疗，无论是一线治疗还是治疗耐药的情况下。encorafenib 是最新获得 FDA 批准的与 MEK 抑制剂 binimetinib 联合使用的 BRAF 抑制剂。
作者概述了导致 encorafenib 在 BRAFV600 突变黑色素瘤中应用的临床前开发和临床试验。他们还讨论了其在临床实践中的当前应用，提供了他们对此主题的专业观点。
临床前研究为将 encorafenib 的研究升级为临床开发/测试提供了充分的理由。然而，目前还没有足够的数据来确定 encorafenib 与同类药物相比可能的定位，正在进行的试验将进一步确定其在黑色素瘤治疗中的作用。值得注意的是，正在进行的研究进一步探索了 encorafenib + binimetinib 的作用，例如与免疫治疗药物联合的方案，以及脑转移。
