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

Abstract

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.