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

Expert Opin Drug Saf. 2023 Jul-Dec;22(12):1309-1316. doi: 10.1080/14740338.2023.2245324. Epub 2023 Aug 12.

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; FDA adverse event reporting system; disproportionality analysis; interstitial lung disease; real-world study.

MeSH terms

  • Anaplastic Lymphoma Kinase / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Crizotinib / adverse effects
  • Humans
  • Lung Diseases, Interstitial* / chemically induced
  • Lung Neoplasms* / drug therapy
  • Pharmacovigilance
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Tyrosine Kinases
  • Tyrosine Kinase Inhibitors

Substances

  • Crizotinib
  • Anaplastic Lymphoma Kinase
  • Tyrosine Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • Protein Kinase Inhibitors