Medical Oncology of Melanoma & Sarcoma Unit, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy.
Medical Oncology Unit of Respiratory Tract, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy.
Future Oncol. 2017 Dec;13(29):2629-2644. doi: 10.2217/fon-2017-0262. Epub 2017 Sep 11.
The discovery of ALK rearrangement in non-small-cell lung cancer (NSCLC) triggered rapid clinical development of a family of specific drugs targeting this alteration, called ALK inhibitors. Despite high rate of responses, the vast majority of patients treated with first-generation ALK inhibitor crizotinib will ultimately develop disease progression. The second-generation ALK inhibitor, ceritinib, is an oral, small-molecule that inhibits the ALK kinase activity with a potency 20-fold greater than crizotinib, being able to tackle some of the principal mechanisms of resistance to crizotinib. Evidences from five large prospective clinical trials have so far showed impressive activity of ceritinib in ALK inhibitor pretreated and naive NSCLC patients. This review will focus on the preclinical and clinical data available regarding ceritinib pharmacology, clinical efficacy and safety profile.
间变性淋巴瘤激酶（ALK）重排在非小细胞肺癌（NSCLC）中的发现，促使针对该变异的一系列特定药物（即 ALK 抑制剂）迅速进入临床研发。尽管反应率很高，但接受第一代 ALK 抑制剂克唑替尼治疗的绝大多数患者最终都会出现疾病进展。第二代 ALK 抑制剂色瑞替尼是一种口服的小分子药物，其对 ALK 激酶的抑制活性比克唑替尼强 20 倍，能够解决克唑替尼耐药的一些主要机制。迄今为止，五项大型前瞻性临床试验的证据表明，色瑞替尼在 ALK 抑制剂预处理和初治 NSCLC 患者中具有显著的活性。这篇综述将重点介绍色瑞替尼的药理学、临床疗效和安全性概况的相关临床前和临床数据。
