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The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis

Authors Hou H, Sun D, Liu K, Jiang M, Liu D, Zhu J, Zhou N, Cong J, Zhang X

Received 8 October 2018

Accepted for publication 12 March 2019

Published 7 May 2019 Volume 2019:11 Pages 4109—4118

DOI https://doi.org/10.2147/CMAR.S190098

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Lu-Zhe Sun


Helei Hou,* Dantong Sun,* Kewei Liu, Man Jiang, Dong Liu, Jingjuan Zhu, Na Zhou, Jing Cong, Xiaochun Zhang

Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of China

*These authors contributed equally to this work


Background: A total of 2%–7% of non-small cell lung cancer (NSCLC) patients have anaplastic lymphoma kinase (ALK) mutations. At present, three or more generations of ALK inhibitors have been used for ALK-positive NSCLC treatment, including crizotinib, alectinib, ceritinib, and brigatinib. Although most adverse events (AEs) of ALK inhibitors are grades 1 to 2 and generally can be well tolerated, serious adverse events (SAEs) of ALK inhibitors lack data analysis, and the lung toxicity of ALK inhibitors needs attention. Thus, we performed this meta-analysis to evaluate the safety of ALK inhibitors, especially in terms of drug-related SAEs.
Methods: A total of 19 studies from 4 databases (PubMed, Science Direct, ClinicalTrials.gov and Cochrane Library) were included in this meta-analysis. All statistical analyses in this meta-analysis were performed with the STATA 14.0 software. We analyzed the incidences of total AEs, total SAEs and SAEs for different ALK inhibitors.
Results: AEs of the ALK inhibitors occurred in almost all participants, and SAEs occurred in more than 20% of the participants. For ceritinib and brigatinib, SAEs occurred in more than 40% of the participants. Alectinib is most likely the safest of the two generations of ALK inhibitors. Generally, the ALK inhibitors showed significant lung toxicity.
Conclusion: In conclusion, attention should be focused on ALK inhibitor-related SAEs, especially lung toxicity. According to this meta-analysis, alxectinib seems to be the safest ALK inhibitor. Physicians should focus on the related SAEs when prescribing ALK inhibitors.

Keywords: ALK inhibitors, safety, serious adverse events, lung toxicity

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