Risk of venous thromboembolism with CDK4/6 inhibitor use in breast cancer: a systematic review and meta-analysis.

Hormone receptor-positive (HR+), HER2-negative, non-metastatic breast cancer represents a significant proportion of early-stage breast cancer. The introduction of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors combined with endocrine therapy (ET) have significantly improved disease-free survival. Existing studies suggest that CDK4/6 inhibitors are associated with an increased risk of venous thromboembolism (VTE). We further studied this risk. The databases Medline, Embase, and Cochrane Central Register of Controlled Trials (Central) were searched. 4624 publications were screened for inclusion, and seven studies were selected for data extraction and analysis. Publications included studied patients who had a diagnosis of non-metastatic breast cancer and received treatment with CKD 4/6 inhibitors. Major exclusion criteria included age <18 years-old, metastatic cancer, and patients already diagnosed with a hypercoagulable disorder. The statistical analysis was performed using RevMan 9.19.0. We reported information in risk ratio (RR) and pooled the information with a random-effects meta-analysis according to the heterogeneity expected. We observed the incidence of VTE in the group of patients treated with CDK4/6 inhibitors to be larger (68/3165) than the incidence of VTE in patients treated with ET alone (11/2205). We found the relative risk of developing VTE was significantly higher with CDK4/6 inhibitor treatment than with treatment with ET alone (RR 3.8, 95% CI, 2.0-7.2). Overall, there was not a significant variability in effect estimates from the included studies (I2 = 0%). As the use of CDK4/6 grows, this information will help conversations about risks and benefits when selecting treatment plans.