Cardiovascular adverse events associated with EGFR and HER2 dual TKIs: a pharmacovigilance study based on the FAERS database.

Background: EGFR and HER2 dual TKIs have been approved for the treatment of advanced breast cancer in patients who are HER2-positive for second and/or third-line treatment. However, there is a lack of attention to the cardiovascular adverse events (AEs) caused by EGFR and HER2 dual TKIs.

Research design and methods: We analyzed data spanning between March 2007 and June 2024 using the FAERS database and the reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network to perform disproportionality analysis.

Results: Compared with non-cardiovascular AEs, cardiovascular AEs were associated with more severe clinical outcomes, such as higher rates of hospitalization, life-threatening events, disability, and death. Our analysis revealed that lapatinib had a higher-than-expected reporting rate for three SMQs, including cardiac failure, embolic and thrombotic events, and cardiomyopathy. No significant cardiovascular signals were observed for neratinib.

Conclusion: Disproportionality analysis results revealed a positive signal for cardiac failure, embolic and thrombotic events, and cardiomyopathy of lapatinib, and no positive signal for neratinib. We should pay attention to high-risk signals in clinical practice and monitor them appropriately.