# Hepatotoxicity associated with anti-neoplastic agents: a pharmacovigilance analysis of the Food and Drug Administration Adverse Event Reporting System database

## TL;DR

This study analyzed reports of liver damage caused by cancer drugs using FDA data, finding that some drugs are strongly linked to severe liver toxicity, especially in the first month of treatment.

## Contribution

The study identifies 56 anti-neoplastic agents with hepatotoxicity signals and highlights methodological limitations in pharmacovigilance data interpretation.

## Key findings

- Mercaptopurine, pegaspargase, and blinatumomab showed the highest risk of hepatotoxicity.
- 14.95% of patients experienced fatal or life-threatening outcomes from drug-induced liver injury.
- Most adverse events occurred within the first month of treatment, with faster onset in fatal cases.

## Abstract

Hepatotoxicity is commonly observed in patients undergoing chemotherapy. However, the clinical features and outcomes of hepatotoxicity associated with anti-neoplastic agents remain unclear. In this study, we investigated the characteristics and risk factors of hepatotoxicity associatedwith anti-neoplastic agents.

We conducted a retrospective pharmacovigilance analysis using data acquired from the FDA Adverse Event Reporting System (FAERS) database (Q1–2004 to Q3 2024). Hepatotoxicity risk was assessed by disproportionality analysis, while LASSO and multivariate logistic regression were applied to control for potential confounders. Finally, we analyzed the time duration to the onset of hepatotoxicity.

A total of 56 anti-neoplastic agents exhibited positive signals for hepatotoxicity, involving 4,195 reports. Female patients (46.50%) were more frequently affected than males (26.70%), with a median age of 56 years. 627 patients (14.95%) experienced fatal or life-threatening outcomes. The top three drugs with the highest Reporting Odds Ratio (ROR) values were mercaptopurine (ROR = 26.57), pegaspargase (ROR = 13.67) and blinatumomab (ROR = 11.93). Most events occurred within the first month (44.18%) and the median TTO value in the Fatal group (22.5 days) was shorter than that in the non-fatal group (42 days) (p < 0.05). Furthermore, Weibull shape parameter (WSP) analysis indicated that 20 of the top 30 drugs were random failure models.

This analysis profiles hepatotoxicity signals for anti-neoplastic agents but reveals a major methodological gap: without using a validated causality tool like the updated RUCAM, FAERS data cannot confirm druginduced liver injury (DILI). Future studies should integrate RUCAM to improvespecificity and clinical relevance.

Pharmacovigilance analysis of hepatotoxicity associated with anti-neoplastic agents using the FAERS database from 2004 Q1 to 2025 Q1. Methods include descriptive analysis, disproportionality analysis, time to onset, and multivariate logistic regression. Core findings highlight 11 of 56 agents lacking warnings, fatal outcomes in 14.95% of patients, and most adverse events occurring within the first treatment month. Top ROR drugs are mercaptopurine, pegaspargase, and blinatumomab. Recommendations suggest monitoring liver function during chemotherapy.