Avrillon Virginie, Pérol Maurice
Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France.
Future Oncol. 2017 Feb;13(4):321-335. doi: 10.2217/fon-2016-0386. Epub 2016 Oct 26.
Alectinib is a highly selective second-generation ALK inhibitor that is active against most crizotinib ALK resistance mutations, with a good penetration in CNS and a good safety profile. Thanks to the positive results of Phase II trials, alectinib was approved in Japan and by the US FDA for ALK-positive non-small-cell lung cancer (NSCLC) patients pretreated with crizotinib. Recently, the Phase III J-ALEX study demonstrated superiority of alectinib over crizotinib in crizotinib naive ALK-positive NSCLC, with an impressive improvement of progression-free survival. From the results and those expected of Phase III ALEX study, alectinib might become the frontline treatment of ALK-positive NSCLC. This article summarizes the therapeutic options in ALK-positive advanced NSCLC, and the chemical, pharmacodynamics, pharmacokinetics, metabolism and clinical efficacy of alectinib.
阿来替尼是一种高度选择性的第二代ALK抑制剂，对大多数克唑替尼耐药的ALK突变具有活性，在中枢神经系统中具有良好的渗透性且安全性良好。由于II期试验的阳性结果，阿来替尼在日本和美国被美国食品药品监督管理局批准用于接受过克唑替尼治疗的ALK阳性非小细胞肺癌（NSCLC）患者。最近，III期J-ALEX研究证明，在初治的ALK阳性NSCLC患者中，阿来替尼优于克唑替尼，无进展生存期有显著改善。从III期ALEX研究的结果及预期来看，阿来替尼可能会成为ALK阳性NSCLC的一线治疗药物。本文总结了ALK阳性晚期NSCLC的治疗选择以及阿来替尼的化学性质、药效学、药代动力学、代谢情况和临床疗效。
