Key result
Lapatinib showed a higher-than-expected reporting rate for cardiac failure, embolic/thrombotic events, and cardiomyopathy, while no significant cardiovascular signals were observed for neratinib.
Why the study?
EGFR and HER2 dual TKIs are approved for advanced HER2-positive breast cancer, but there is a lack of attention to their cardiovascular adverse events.
Are EGFR and HER2 dual TKIs associated with an increased risk of cardiovascular adverse events?
Observational
Are EGFR and HER2 dual TKIs associated with an increased risk of cardiovascular adverse events?
Lapatinib, but not neratinib, is associated with significant cardiovascular safety signals including heart failure and thromboembolic events in real-world pharmacovigilance data.
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.
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Qin et al. (2025) conducted an observational in Advanced breast cancer (HER2-positive). EGFR and HER2 dual TKIs (lapatinib, neratinib) vs. Expected reporting rate (disproportionality analysis) was evaluated on Cardiovascular adverse events (cardiac failure, embolic and thrombotic events, and cardiomyopathy). Lapatinib showed a higher-than-expected reporting rate for cardiac failure, embolic/thrombotic events, and cardiomyopathy, while no significant cardiovascular signals were observed for neratinib.
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