Liver injury related to vascular endothelial growth factor tyrosine kinase inhibitors: a pharmacovigilance analysis of the USA FDA adverse event reporting system (FAERS) database.

Abstract

Background: While vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKIs) are known to cause adverse events like cardiotoxicity and haematotoxicity, their impact on liver injury remains understudied. This study evaluates the association between VEGFR-TKIs and liver injury using data from the FDA Adverse Event Reporting System (FAERS) database from 2006 to 2024.

Research design and methods: Nine VEGFR-TKIs (Axitinib, Vandetanib, Cabozantinib, Lenvatinib, Pazopanib, Ponatinib, Regorafenib, Sunitinib, Sorafenib) were analyzed. Disproportionality and Bayesian analyses identified cases of VEGFR-TKI-induced liver injury, assessing onset time, mortality, and hospitalization rates.

Results: 8,619 cases of liver injury were identified. Pazopanib had the highest association with liver injury (reporting odds ratio 3.9). The median onset of liver injury was 21 days. Mortality was 28.5%, with Sorafenib linked to the highest mortality (48.6%). Lenvatinib had the highest hospitalization rate (56%).

Conclusion: VEGFR-TKIs are associated with liver injury. Close monitoring is required to mitigate the risks of hospitalization and early mortality during treatment.