Interstitial lung disease risk of anaplastic lymphoma kinase tyrosine kinase inhibitor treatment of non-small cell lung cancer: a real-world pharmacovigilance study

ABSTRACT

Background

Interstitial lung disease (ILD) is a rare but life-threatening and fatal treatment-related pneumonitis. This study investigated the association between anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) and ILD.

Research design and Methods

Cases of ILD that developed after treatment with an ALK-TKI in the Food and Drug Administration’ s Adverse Event Reporting System (FAERS) data were assessed. We also described the clinical features of these cases and evaluated onset time, hospitalization, life-threatening condition, and fatality rate of ILD developed after treatment with an ALK-TKI.

Results

All five ALK-TKI regimens were significantly associated with ILD. The median onset time to ILD was significantly different for brigatinib, crizotinib, alectinib, lorlatinib, and ceritinib: 4.5, 25, 35.5, 54.5, and 84 days, respectively. ALK-TKI-associated ILD resulted in hospitalization in 55.77% of patients and death or life-threatening outcomes in 43.03%. The highest and lowest proportions of ILD-related fatalities were observed after crizotinib and alectinib treatment, respectively.

Conclusions

ALK-TKIs were associated with ILD; therefore, the risk of developing ILD after treatment with an ALK-TKI should be carefully considered in clinical settings.

KEYWORDS:

• Anaplastic lymphoma kinase tyrosine kinase inhibitors
• disproportionality analysis
• FDA adverse event reporting system
• interstitial lung disease
• real-world study

Acknowledgments

We thank Yabo Ren, Mengna Wang, and Yinxiao Du for their insightful suggestions. We would like to thank Editage (www.editage.cn) for English language editing.

Declaration of interests

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

Min Zhao and Jiang Li designed the study. Shu Liu analyzed and interpreted the data. Min Zhao generated the figures/tables and drafted the manuscript. Rui Xie and Jianjun Zhang reviewed and corrected the manuscript. All authors contributed to the article and approved the submitted version. All authors agree to be accountable for all aspects of the work.

Data availability statement

The datasets analyzed during the current study are available in the following resource available in the public domain: https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html. The original contributions presented in the study are included in the article and its supplementary materials. Further inquiries can be directed to the corresponding author.

Institutional review board statement

Ethical review and approval were waived for this study because it is based on anonymous data that can be downloaded from a publicly available source.

Additional information

Funding

This manuscript was funded by the Zhejiang Pharmaceutical Association (No. 2022ZYY27) and Zhejiang Medical Doctors Association (No. YS2022-3-013).