Tyrosine Kinase Inhibitor-Related Hepatotoxicity in Patients with Advanced Lung Adenocarcinoma: A Real-World Retrospective Study

Purpose: Hepatic injury is a common side effect following tyrosine kinase inhibitor (TKI) therapy and our understanding usually comes from clinical trials. In this retrospective study, we aimed to investigate the characteristics, risk factors and regimen-related differences of epidermal growth factor receptor (EGFR)-TKI-related hepatic toxicity in patients with advanced lung adenocarcinoma (LAD).

Patients and methods: Liver function tests were documented in 424 patients admitted into the Shanghai Chest Hospital between January 2014 and December 2016 with advanced (IIIB/IV) LAD who received first-line gefitinib, erlotinib or icotinib. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. The clinical spectrum and onset time of hepatic injury were evaluated. The risk factors of hepatic dysfunction were determined using a logistic regression analysis.

Results: A total of 87 (20.5%) patients experienced hepatotoxicity and 5.7% were of grade 3/4 liver dysfunction. The median onset time of hepatotoxicity was 7 weeks. Presence of hepatitis virus (HR: 2.593, 95% CI: 1.090-6.170, P=0.031) and pretreatment liver impairment (HR: 3.460, 95% CI: 1.746-6.855, P<0.001) were risk factors associated with increased risk of hepatotoxicity. Gefitinib (HR: 1.872, 95% CI: 1.028-3.412, P=0.040) and erlotinib (HR: 3.578, 95% CI: 1.683-7.609, P=0.001) had increased risk of hepatotoxicity compared to icotinib.

Conclusion: The different toxic profile of EGFR-TKIs should be taken into account in the choice of treatment based on the patients' comorbidity.