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Toxicity profile of anaplastic lymphoma kinase tyrosine kinase inhibitors for patients with non-small cell lung cancer: A systematic review and meta-analysis

Abstract

Anaplastic lymphoma kinase (ALK) inhibitors are commonly used for patients harboring ALK-positive non-small cell lung cancer (NSCLC). This meta-analysis was conducted to evaluate the toxicity profile of ALK inhibitors. Pubmed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases were systematically searched for clinical trials conducted in advanced NSCLC treated with ALK inhibitors. The incidences of pooled adverse events (AEs) were conducted using the random effects model. We included 30 studies in the meta-analysis. Almost all patients receiving ALK inhibitor monotherapy occurred at least one AE. The pooled incidences of grade ≥ 3 AEs were 71.3% for ceritinib 750 mg, 44.6% for crizotinib, 37.4% for alectinib, and 35.3% for ensartinib. Only one study each reported the incidence of grade ≥ 3 AEs for brgatinib (72.8%), lorlatinib (72.4%), and ceritinib 450 mg (64.8%), respectively. The rates of dose reduction due to AEs ranking from high to low were ceritinib 750 mg, brigatinib, ceritinib 450 mg, lorlatinib, crizotinib, ensartinib, and alectinib. The rates of treatment discontinuation due to AEs were low, ranging from 3.8% to 10.5%. Gastrointestinal AEs were most common for ceritinib 750 mg. Hepatic transaminases elevation was mostly observed in ceritinib and brigatinib. Rash frequently occurred for ensartinib. Lorlatinib had a high incidence of hypertriglyceridemia and hypercholesterolemia, which were rarely reported in other ALK inhibitors. The incidences of grade ≥ 3 AEs for individual ALK inhibitor were moderately high yet manageable. Different toxicity spectrums were found in each ALK inhibitor.

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Data availability

All data relevant to the study are included in the article or uploaded as supplemental information.

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Funding

This work was supported by China National Major Project for New Drug Innovation (2017ZX09304015).

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Conception, design and supervision: Yuankai Shi Acquisition of data: Yunxia Tao, Yu Zhou, Le Tang, Haizhu Chen Analysis and interpretation of data: Yunxia Tao, Yu Zhou, Le Tang, Yu Feng, Yuankai Shi Manuscript draft and editing: Yunxia Tao, Yu Zhou, Le Tang Review and revision of the manuscript: Yunxia Tao, Yu Zhou, Le Tang, Yuankai Shi.

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Correspondence to Yuankai Shi.

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Tao, Y., Zhou, Y., Tang, L. et al. Toxicity profile of anaplastic lymphoma kinase tyrosine kinase inhibitors for patients with non-small cell lung cancer: A systematic review and meta-analysis. Invest New Drugs 40, 831–840 (2022). https://doi.org/10.1007/s10637-022-01242-6

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Keywords

  • Anaplastic lymphoma kinase tyrosine kinase inhibitors
  • Adverse events
  • Non-small cell lung cancer
  • Meta-analysis