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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
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