Cardiotoxicity of newer HER2-Directed therapies in breast cancer: A systematic review and meta-analysis of incidence and comparative risk
Abstract
PURPOSE: This systematic review and meta-analysis aimed to estimate the incidence and comparative risk of cardiotoxicity associated with newer HER2-targeted therapies compared with conventional trastuzumab-based regimens. It also evaluates the differences across drug classes, clinical subgroups, and monitoring strategies.
MATERIALS AND METHODS: PubMed, Embase, CENTRAL, and Scopus were searched (2005-2025) for randomized controlled trials (RCTs) and prospective studies reporting cardiac outcomes with HER2-directed therapies. Pooled cardiotoxicity incidence was calculated from single-arm studies and intervention arms of RCTs and risk ratios (RRs) from RCTs using random-effects models. Subgroup analyses were performed by drug class, anthracycline exposure, HER2 category, age, and cardiac monitoring frequency. Certainty of evidence was assessed using GRADE.
RESULTS: Fifty-eight studies (35,984 patients) were included. Pooled cardiotoxicity incidence was 5.08% (95% CI, 3.37 to 7.58) with left ventricular ejection fraction (LVEF) decline in 4.68% patients, and other cardiac events were each reported in 0.05).
CONCLUSION: Newer HER2-directed therapies demonstrate low cardiotoxicity, with rare serious events and no evidence of excess risk compared with conventional trastuzumab-based regimens. These findings support cardiac safety but suggest the need for standardized monitoring and uniform cardiotoxicity definitions.
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 35,984 participants or records.
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