Thromboembolism profiles associated with cyclin-dependent kinase 4/6 inhibitors: a real-world pharmacovigilance study and a systematic review

Abstract

ABSTRACT Background Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and thrombosis. Research design and methods A retrospective pharmacovigilance analysis based on real-world data combined with a systematic review was used to explore the thrombotic risk profiles of CDK4/6i. The study has been registered with Prospero (CRD42021284218). Result In the pharmacovigilance analysis, CDK4/6i showed a higher rate of reported venous thromboembolism (VTE) (ROR = 2.78, 95% CI = 2.64–2.92), with the highest signal for trilaciclib (ROR = 27.55, 95% CI = 13.43–56.52) but only 9 cases, followed by abemaciclib (ROR = 3.73, 95% CI = 3.19–4.37). For arterial thromboembolism (ATE), only ribociclib increased the reporting rate (ROR = 2.14, 95% CI = 1.91–2.41). In the meta-analysis, palbociclib, abemaciclib, and trilaciclib all increased the risk of VTE (OR = 2.23, 3.17, and 3.90). In the subgroup analysis, only abemaciclib increased the risk of ATE (OR = 2.11, 95% CI = 1.12–3.99) . Conclusions CDK4/6i had different profiles of thromboembolism. Palbociclib, abemaciclib, or trilaciclib increased the risk of VTE. Ribociclib and abemaciclib showed a weak association with the risk of ATE.