Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy Versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2-) early-stage breast cancer (esBC) is still to be confirmed.

Methods: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered < 0.05 to be statistically significant.

Results: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; = 0.829).

Conclusions: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2- esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.