CDK4/6 Inhibitors Plus Endocrine Therapy in Early-Stage HR+/HER2- Breast Cancer: Updated Meta-Analysis of Phase III...

This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed.

A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models.

Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i.

The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit.