Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, 1066 CX, The Netherlands.
Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, Maastricht, 6229 HX, The Netherlands.
Future Oncol. 2020 Feb;16(6):161-173. doi: 10.2217/fon-2019-0748.
Approximately 10-15% of colorectal cancers (CRCs) harbor an activating mutation, leading to tumor growth promotion by activation of the mitogen-activated protein kinases pathway. mutations are prognostic for treatment failure after first-line systemic therapy in the metastatic setting. In contrast to the efficacy of combined BRAF and MEK inhibition in melanoma, mutant CRC is intrinsically unresponsive due to upregulation of HER/EGFR. However, combining the EGFR inhibitor cetuximab, the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib improves overall survival. This review discusses the current treatment field for patients with mutant metastatic CRC and summarizes the pharmacology, efficacy and safety of the novel doublet and triplet therapies consisting of encorafenib and cetuximab with or without binimetinib.
约 10-15%的结直肠癌 (CRC) 存在激活突变，通过激活丝裂原活化蛋白激酶途径促进肿瘤生长。在转移性疾病中， 突变与一线系统治疗后的治疗失败相关。与黑色素瘤中联合 BRAF 和 MEK 抑制的疗效相比，由于 HER/EGFR 的上调， 突变 CRC 本质上无反应。然而，联合 EGFR 抑制剂西妥昔单抗、BRAF 抑制剂 encorafenib 和 MEK 抑制剂 binimetinib 可改善总生存期。这篇综述讨论了目前治疗转移性 CRC 患者的方法，并总结了由 encorafenib 和 cetuximab 组成的新型双药和三药治疗方案的药理学、疗效和安全性，以及是否联合 binimetinib。
