Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC

BMC Cancer

Research Article

Hao Hu¹  Chang-Long Chen²  Yan Tang²  Xiao-Fei Zhang²  Jian-Chuan Xia²  Zi-Qi Zhou²  De-Sheng Weng²  Qian Zhu² 

[1] Department of Thoracic Surgery, Medical College of Nanchang University, 330006, Nanchang, People’s Republic of China;State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People’s Republic of China;Department of Biotherapy, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, People’s Republic of China;

关键词: Crizotinib;    Ceritinib;    Alectinib;    Anaplastic lymphoma kinase;    Tyrosine kinase inhibitors;    Non-small-cell lung cancer;   

DOI  :  10.1186/s12885-017-3405-3

 received in 2016-08-14, accepted in 2017-06-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. However, the differences in the toxicity profiles among these drugs are still unclear.MethodsWe performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs’ inception to May 2016 to identify clinical trials. Severe adverse events (AEs) (grade ≥ 3) based on the ALK-TKI type were analysed.ResultsSeventeen trials published between 2011 and 2016, including a total of 1826 patients, were eligible for analysis. Patients in 10 trials (n = 1000) received crizotinib, patients in 5 trials (n = 601) received ceritinib and patients in 2 trials (n = 225) received alectinib. The overall frequencies of treatment-related death and AEs due to treatment withdrawal were 0.9% (12/1365) and 5.5% (85/1543), respectively. Moreover, the frequency of severe AEs in patients treated with ceritinib was significantly higher than patients treated with crizotinib or alectinib, especially for hepatotoxicity, fatigue and some of gastrointestinal symptoms. Additionally, significant difference in the elevated lipase and amylase levels (grade ≥ 3) were detected between ceritinib and crizotinib/alectinib, whereas neutropenia was less frequent.ConclusionsALK-TKIs were safe for ALK-positive patients. Moreover, statistically significant differences in some severe AEs among ceritinib, crizotinib and alectinib were detected in present study.

【 授权许可】

CC BY   
© The Author(s). 2017