Cardiac adverse events associated with axitinib: A real-world pharmacovigilance study based on the Japanese adverse drug event report database

Clinical Snapshot

Key Findings

• P Value: Statistical significance achieved for 16 cardiac AEs

• Effect Size: RORs calculated but specific values not provided in abstract

• Primary Outcome: 16 cardiac adverse events showed disproportionality signals with axitinib

• Nnt Or Sensitivity: 508 cardiac AEs among 4,788 total axitinib reports (10.6% cardiac AE rate)

• Confidence Interval: Not reported in abstract

Clinical Application

Findings support enhanced cardiac monitoring protocols during axitinib therapy Relevant to Australian oncology practice as axitinib is PBS-listed for advanced renal cell carcinoma. Supports TGA post-marketing surveillance and COSA guidelines for tyrosine kinase inhibitor monitoring Patients receiving axitinib for renal cell carcinoma or other approved indications

Abstract

OBJECTIVE: To evaluate the disproportionality, times to onset, and outcomes of cardiac adverse events (AEs) associated with axitinib, using data from the Japanese Adverse Drug Event Report (JADER) database. METHODS: We analyzed data for the period from April 2004 to December 2024. Those on cardiac AEs were extracted and the disproportionality of axitinib-associated AEs was assessed by calculating reporting odds ratios (RORs). RESULTS: Of the 2,988,681 reports with sex and age information, we identified 4788 reports of AEs associated with axitinib, including 508 cardiac AEs. Signals were detected for 16 cardiac AEs after adjustment for sex and age. Fatal outcomes were reported for five of these events with particularly high rates observed for cardiac failure, myocarditis, and immune-mediated myocarditis. Median times to onset indicated that cardiac AEs associated with axitinib occurred 14 to 420 days after administration. Weibull distributions showed that seven AEs (blood pressure increased, myocardial infarction, acute myocardial infarction, blood pressure systolic increased, oedema peripheral, oedema, and generalised oedema) occurred constantly throughout the exposure period (random failure type), and stress cardiomyopathy and immune-mediated myocarditis developed in a dose-dependent manner (wear-out failure-type). CONCLUSIONS: We focused on cardiac AEs associated with axitinib as post-marketing AEs. Some with fatal outcomes may occur not only early in treatment but also later in the course. Continuous monitoring is essential to ensure timely detection and management of these potentially serious AEs in clinical practice.