Cardiac arrhythmias associated with anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS)

ABSTRACT

Background

Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) may provoke cardiac arrhythmias. We conducted this pharmacovigilance analysis to research cardiac arrhythmias associated with ALK-TKIs using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Research design and methods

The first ALK-TKI, named crizotinib, was approved by the Food and Drug Administration (FDA) on 26 August 2011 for the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). We evaluated ALK-TKIs-induced cardiac arrhythmias, by using the reporting odds ratio (ROR) and information component (IC) for mining the adverse event report signals in the FAERS database between January 2016 and June 2022.

Results

We identified a total of 362 ALK-TKIs-related cardiac arrhythmia reports which appeared to influence more men (64.44%) than women (30.76%), with a median age of 68 (interquartile range [IQR] 7–74) years. Compared with the full database, ALK-TKIs were detected with pharmacovigilance of cardiac arrhythmias (ROR025 = 1.26, IC025 = 0.26). Crizotinib and alectinib were found to be related to higher reporting of arrhythmias. The median time to onset (TTO) among five ALK-TKI therapies was significantly different (p = 0.044).

Conclusion

ALK-TKIs present different frequencies of cardiac arrhythmias reporting, with only crizotinib and alectinib producing positive signals in high-level group term (HLGT) level arrhythmia. The time interval between the initial of drug treatment to the onset of arrhythmia varies greatly and cannot be predicted.

KEYWORDS:

• Cardiac arrhythmias
• anaplastic lymphoma kinase tyrosine kinase inhibitors
• non-small cell lung cancer
• adverse event reporting system
• FAERS

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 contribution statement

FF Wang and GS Xu designed and wrote the manuscript. FF Wang and XA Wu performed the data acquisition, statistical analysis, and revising. All other authors participated in the interpretation of the results. The final manuscript was read, checked, and approved by all authors.

Acknowledgments

This study was performed using the FDA Adverse Event Reporting System (FAERS) database that was provided by the FDA. The information, results, or interpretation of the current study do not represent any opinion of the FDA.

Additional information

Funding

This paper was not funded.