Department of Oncology, Antwerp University Hospital , Edegem, Belgium.
Faculty of Health Sciences en Medicine, University of Antwerp , Antwerp, Belgium.
Expert Opin Pharmacother. 2020 May;21(7):747-754. doi: 10.1080/14656566.2020.1729122. Epub 2020 Feb 26.
Approximately 50% of patients with metastatic melanoma have mutations in BRAF. Based on the results of prior phase III trials, the combination of a BRAF inhibitor (BRAFi) and a MEK inhibitor (MEKi) is the standard of care in patients with BRAF-mutant metastatic melanoma.
The author summarizes the available data on binimetinib, a reversible inhibitor of the kinase activity of MEK1 and MEK2, in BRAF- and NRAS-mutated melanoma.
With the advent of binimetinib and encorafenib, clinicians can choose between three BRAFi/MEKi combinations. Indirect comparison and a network meta-analysis suggest that binimetinib plus encorafenib is at least as active as the other two BRAFi/MEKi combinations and that safety is similar. The choice should be guided by the slightly different toxicity profile, local availability, and product experience. The optimal sequence of immunotherapy and BRAFi/MEKi in patients with BRAF-mutated tumors is unclear. As the response to BRAF/MEK inhibition is usually prompt and response to immunotherapy can be delayed, clinicians often choose a BRAFi/MEKi combination as first-line therapy in patients with rapidly evolving and threatening disease. Single-agent binimetinib almost doubled median progression-free survival when compared to dacarbazine in patients with NRAS-mutated melanoma.
约 50%的转移性黑色素瘤患者存在 BRAF 突变。基于先前的 III 期临床试验结果，BRAF 抑制剂（BRAFi）和 MEK 抑制剂（MEKi）联合治疗 BRAF 突变转移性黑色素瘤患者是标准治疗方案。
作者总结了 MEK1 和 MEK2 激酶活性可逆抑制剂 binimetinib 在 BRAF 和 NRAS 突变黑色素瘤中的现有数据。
随着 binimetinib 和 encorafenib 的出现，临床医生可以在三种 BRAFi/MEKi 联合治疗方案中进行选择。间接比较和网络荟萃分析表明，binimetinib 加 encorafenib与其他两种 BRAFi/MEKi 联合治疗方案一样有效，安全性相似。选择应根据略有不同的毒性特征、当地可用性和产品经验来指导。在存在 BRAF 突变肿瘤的患者中，免疫治疗与 BRAFi/MEKi 的最佳序贯治疗尚不清楚。由于 BRAF/MEK 抑制的反应通常迅速，而免疫治疗的反应可能延迟，因此临床医生通常会选择 BRAFi/MEKi 联合治疗方案作为快速进展和威胁生命疾病患者的一线治疗。与达卡巴嗪相比，单药 binimetinib 使 NRAS 突变黑色素瘤患者的中位无进展生存期几乎翻倍。
