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

ObjectiveCyclin-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 sourceA literature search was conducted using PubMed, ClinicalTrials.gov, and manual searches of relevant articles.Study selectionStudies included in this review were those that reported CDK4/6 inhibitor cardiovascular outcomes, specifically QTc prolongation and thrombosis, in patients with advanced breast cancer.ConclusionThe 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.