Newer HER2-directed therapies demonstrated no significant difference in cardiotoxicity compared with conventional trastuzumab-based regimens (RR 0.97; 95% CI 0.73 to 1.29).
Meta-Analysis (n=35,984)
Do newer HER2-directed therapies increase the risk of cardiotoxicity compared to conventional trastuzumab-based regimens in patients with breast cancer?
Newer HER2-directed therapies demonstrate low cardiotoxicity with no evidence of excess risk compared to conventional trastuzumab-based regimens, supporting their cardiac safety profile.
Relative Risk: 0.97 (95% CI 0.73–1.29)
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.
Sundaramoorthy et al. (2026) conducted a meta-analysis in Breast Cancer (n=35,984). Newer HER2-directed therapies vs. Conventional trastuzumab-based regimens was evaluated on Cardiotoxicity (RR 0.97, 95% CI 0.73 to 1.29). Newer HER2-directed therapies demonstrated no significant difference in cardiotoxicity compared with conventional trastuzumab-based regimens (RR 0.97; 95% CI 0.73 to 1.29).