Cardiovascular safety of CDK4/6 inhibitors in advance breast cancer: Assessing risks of QTc prolongation and thrombosis

Objective Cyclin-dependent kinase (CDK) 4/6 inhibitors have become a cornerstone in the treatment of hormone receptor-positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-) breast cancer, demonstrating significant efficacy in both early and metastatic stages. However, despite their clinical benefits, emerging evidence from health databases, real-world studies, and case reports highlight potential cardiovascular risks, including QTc prolongation and thrombosis. This review aims to comprehensively evaluate the cardiovascular safety profiles of the three FDA-approved CDK4/6 inhibitors—palbociclib, ribociclib, and abemaciclib—in patients with HR+/HER2- advanced breast cancer. Specifically, it compares the risks of QTc prolongation and thrombosis associated with these agents. Data source A literature search was conducted using PubMed, ClinicalTrials.gov, and manual searches of relevant articles. Study selection Studies included in this review were those that reported CDK4/6 inhibitor cardiovascular outcomes, specifically QTc prolongation and thrombosis, in patients with advanced breast cancer. Conclusion The review highlights significant differences in the cardiovascular safety profiles of CDK4/6 inhibitors. Ribociclib is associated with the highest risk of QTc prolongation, with incidence rates ranging from 4.5% to 13.3% in RCTs, while palbociclib demonstrates a more favorable profile, with QTc prolongation reported in less than 1% of cases. Abemaciclib, although not linked to QTc prolongation, has the highest reported incidence of thrombosis, ranging from 2.0% to 4.9% in RCTs. Real-world data revealed thrombosis incidence rates as high as 17% among patients treated with CDK4/6 inhibitors. Thus, future research must ascertain the cardiovascular safety profiles of different CDK4/6 inhibitors and develop effective cardiovascular toxicity prevention strategies.