Risks of cardiovascular toxicities associated with ALK tyrosine kinase inhibitors in patients with non-small-cell lung cancer: a meta-analysis of randomized control trials

ABSTRACT

Background

Anaplastic lymphoma kinases (ALK) tyrosine kinase inhibitors (TKIs) are effective and safe targeted therapies used in advanced ALK-positive non-small cell lung cancers (NSCLC). However, ALK-TKIs associated cardiovascular toxicities in patients with ALK-positive NSCLCremain incompletely characterized. We conducted the first meta-analysis to investigate this.

Research design and methods

To determine the cardiovascular toxicities associated with these agents, we carried out a meta-analysis comparing ALK-TKIs with chemotherapy and a meta-analysis comparing crizotinib with other ALK-TKIs. Statistical analysis was conducted to calculate the RRs and 95% confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of the included studies.

Results

A total of 11 studies (2855 patients) were included. ALK-TKIs ranked to have more severe cardiovascular toxicities than chemotherapy (RR 5.03, 95% CI 1.97–12.84, P = 0.0007) . Compared with other ALK-TKIs, increased risks of cardiac disorders and VTEs associated with crizotinib were found (cardiac disorders RR 1.75, 95% CI 1.07–2.86, P = 0.03; risk of VTEs RR 3.97, 95% CI 1.69–9.31, P = 0.002; respectively).

Conclusion

ALK-TKIs were associated with higher risks of cardiovascular toxicities. Special attention should be given to the risks of cardiac disorders and VTEs related to crizotinib therapy.

KEYWORDS:

• ALK TKIs
• non-small cell lung cancer
• cardiac disorders
• venous thromboembolic events
• hypertension

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

This study was conceived and designed by Y Zhang. The data acquisition, statistical analysis, article drafting, and revising were performed by J Zhao and Z Ma. H Li, D Sun, Y Hu and C Zhang helped perform the analysis with constructive discussions. All authors participated in the interpretation of the results. The final manuscript was read, checked, and approved by all authors.

Availability of data and material

All datasets presented in this study are included in the article/supplementary material or publicly available on the website of Home - ClinicalTrials.gov.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2182284.

Additional information

Funding

This manuscript was funded by grants from the National Natural Science Foundation of China [Grant No. 31770961].