Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Oncology, Jiangxi Provincial People's Hospital, Nanchang, China.
Chemotherapy. 2022;67(2):67-80. doi: 10.1159/000521452. Epub 2021 Dec 14.
Crizotinib and alectinib are the 2 most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC). We compared their antitumor efficacies and adverse effects based on a pooled analysis of the ALEX, ALESIA, and J-ALEX clinical trials.
Seven databases were searched for eligible articles. The primary endpoints included overall survival (OS), progression-free survival (PFS), central nervous system (CNS)-PFS, drug responses, and adverse effects (AEs).
Seven articles on 3 randomized controlled clinical trials (ALEX, ALESIA, and J-ALEX) that included 697 patients were included. Compared with crizotinib, alectinib exhibited superior efficacy in PFS (HR [hazard ratio]: 0.35 [0.25-0.49], p < 0.00001), OS (HR: 0.66 [0.47-0.92], p = 0.02), CNS-PFS (HR: 0.17 [0.11-0.24], p < 0.00001), duration of response (HR: 0.31 [0.23-0.42], p < 0.00001), objective response rate (risk ratio [RR]: 0.87 [0.80-0.94], p = 0.0003), partial response (RR: 0.88 [0.81-0.96], p = 0.004), and grade 3-5 AEs (RR: 1.43 [1.09-1.87], p = 0.009). Additionally, compared with crizotinib, alectinib exhibited a survival advantage that increased with its prolongation of survival time. The disease control rate, complete response, and total AEs were comparable between the 2 groups. The crizotinib group reported higher rates of constipation, nausea, diarrhea, vomiting, peripheral edema, dysgeusia, visual impairment, and levels of alanine aminotransferase and aspartate aminotransferase as well as greater decreases in appetite and neutrophil count.
In both antitumor efficacy and safety, alectinib appears to be superior to crizotinib for the treatment of ALK-positive NSCLC.
克唑替尼和阿来替尼是治疗间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）的两种最常用的ALK 抑制剂。我们基于 ALEX、ALESIA 和 J-ALEX 临床试验的汇总分析，比较了它们的抗肿瘤疗效和不良反应。
在七个数据库中搜索符合条件的文章。主要终点包括总生存期（OS）、无进展生存期（PFS）、中枢神经系统（CNS）-PFS、药物反应和不良反应（AE）。
纳入了三项随机对照临床试验（ALEX、ALESIA 和 J-ALEX）的七篇文章，共纳入 697 例患者。与克唑替尼相比，阿来替尼在 PFS（HR [风险比]：0.35 [0.25-0.49]，p < 0.00001）、OS（HR：0.66 [0.47-0.92]，p = 0.02）、CNS-PFS（HR：0.17 [0.11-0.24]，p < 0.00001）、缓解持续时间（HR：0.31 [0.23-0.42]，p < 0.00001）、客观缓解率（RR：0.87 [0.80-0.94]，p = 0.0003）、部分缓解（RR：0.88 [0.81-0.96]，p = 0.004）和 3-5 级 AE（RR：1.43 [1.09-1.87]，p = 0.009）方面均具有更好的疗效。此外，与克唑替尼相比，阿来替尼的生存优势随着其生存时间的延长而增加。两组的疾病控制率、完全缓解率和总 AE 相当。克唑替尼组报告的便秘、恶心、腹泻、呕吐、外周水肿、味觉障碍、视力障碍、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高以及食欲和中性粒细胞计数下降的发生率更高。
在抗肿瘤疗效和安全性方面，阿来替尼似乎优于克唑替尼，用于治疗 ALK 阳性 NSCLC。
