Crizotinib versus Alectinib for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

IF 1.7 4区医学 Q3 ONCOLOGY Chemotherapy Pub Date : 2022-01-01 Epub Date: 2021-12-14 DOI:10.1159/000521452

Qinghua Zeng, Xiquan Zhang, Shan He, Zhiyong Zhou, Luping Xia, Wenxiong Zhang, Lin Zeng

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引用次数: 7

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: In both antitumor efficacy and safety, alectinib appears to be superior to crizotinib for the treatment of ALK-positive NSCLC.

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克唑替尼与阿勒替尼治疗alk阳性非小细胞肺癌:系统回顾和荟萃分析

背景:克唑替尼和阿勒替尼是治疗ALK阳性非小细胞肺癌(NSCLC)最常用的两种间变性淋巴瘤激酶(ALK)抑制剂。我们通过对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。方法:在7个数据库中检索符合条件的文章。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)。结果:纳入了3项随机对照临床试验(ALEX、ALESIA和J-ALEX)的7篇文章，共纳入697例患者。与克唑替尼相比，阿勒替尼在PFS (HR[危险比]: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(风险比[RR]: 0.87 [0.80-0.94]， p = 0.0003)、部分缓解(RR: 0.88 [0.81-0.96]， p = 0.004)、3-5级ae (RR: 1.43 [1.09-1.87]， p = 0.009)等方面均表现出更优的疗效。此外，与克唑替尼相比，alectinib表现出随着生存时间的延长而增加的生存优势。两组患者的疾病控制率、完全缓解率和总不良反应发生率具有可比性。克唑替尼组报告便秘、恶心、腹泻、呕吐、外周水肿、认知障碍、视力障碍、丙氨酸转氨酶和天冬氨酸转氨酶水平较高，食欲和中性粒细胞计数下降幅度更大。结论:在抗肿瘤疗效和安全性方面，阿勒替尼治疗alk阳性NSCLC似乎优于克唑替尼。

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来源期刊

Chemotherapy 医学-药学

CiteScore

5.80

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal publishes original research articles and state-of-the-art reviews on all aspects of antimicrobial and antitumor chemotherapy. The results of experimental and clinical investigations into the microbiological and pharmacologic properties of antibacterial, antiviral and antitumor compounds are major topics of publication. Papers selected for the journal offer data concerning the efficacy, toxicology, and interactions of new drugs in single or combined applications. Studies designed to determine the pharmacokinetic and pharmacodynamics properties of similar preparations and comparing their efficacy are also included. Special emphasis is given to the development of drug-resistance, an increasing problem worldwide.