2025/12/16 by Yee-Yin Hoo, Wei-Wei Sia, Sharminii Jaya-Prakason +8
Biochemistry, Genetics and Molecular Biology · Medicine · #Advanced Breast Cancer Therapies #Breast Cancer Treatment Studies #HER2/EGFR in Cancer Research
paper · doi:10.1016/j.ctrv.2025.103069
openalex created_date 2025/12/16 · openalex publication_date 2025/12/16 · openalex updated_date 2026/08/03
BACKGROUND: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) improve survival in HR+/HER2- breast cancer, but agent-specific cardiotoxicity remains a concern. We evaluated the risk of QTc prolongation, and other cardiovascular adverse events (CVAEs) associated with ribociclib, palbociclib, and abemaciclib. METHOD: We conducted a systematic review and meta-analysis (up to May 31st, 2025), assessing QTc prolongation and other CVAEs in patients with HR+/HER2- breast cancer receiving CDK4/6i plus endocrine therapy versus endocrine therapy alone. (PROSPERO: CRD42023460559; UICC Technical Fellowship (TF-20-716796). RESULTS: Twenty-three studies (22 RCTs, 1 cohort) were included. CDK4/6i increased the risk of grade 3/4 QTc prolongation (RR 1.83, 95% CI 1.23-2.74), driven by ribociclib (RR 1.95, 95% CI 1.27-2.98). Palbociclib showed no association, whereas no abemaciclib trials reported QTc data. VTE risk was elevated overall (RR 2.57, 95% CI 1.53-4.32), highest with abemaciclib (RR 5.14, 95% CI 3.09-8.54), while palbociclib was borderline (RR 2.13, 95% CI 0.99-4.57). Subgroup analyses revealed no consistent effect modifiers for ribociclib (QTc) or abemaciclib (VTE). No significant increase was observed for other composite CVAEs (RR 0.99, 95% CI 0.83-1.19) or for individual CVAEs. A hypothesis-generating signal for supraventricular arrhythmias was noted with abemaciclib (RR 3.87, 95% CI 1.19-12.53), based on sparse events. Heterogeneity was low across analyses. CONCLUSION: Our findings mandate drug-tailored rather than class-wide cardiovascular monitoring in patients receiving CDK4/6i: ribociclib warrants routine ECG surveillance, abemaciclib requires intensified monitoring for VTE, and palbociclib shows no consistent signal but still merits vigilance.