Efficacy outcomes of CDK4/6 inhibitors plus endocrine therapy versus chemotherapy in HR+/HER2- breast cancer: A systematic review and meta-analysis.

Abstract

e13065 Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) represent the standard of care for advanced or metastatic HR+/HER2- breast cancer. However, in patients with visceral crises or extensive metastatic disease ( > 3 metastatic sites), the optimal treatment choice between CDK4/6i plus ET and chemotherapy (CT) is not well established. This systematic review and meta-analysis aim to compare the efficacy outcomes overall response rate (ORR), duration of response (DoR), and progression-free survival (PFS) of CDK4/6i plus ET versus CT in this population. Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and conference abstracts from ASCO, SABCS, and ESMO. Key terms included “HR+/HER2- breast cancer,” “CDK4/6 inhibitors,” “chemotherapy,” and “response rate.” Studies reporting ORR, DoR, and PFS outcomes were included. Statistical analysis utilized standardized mean differences (SMD) and hazard ratios (HR) with 95% confidence intervals (95%CI). Results: Of 140 studies identified, 7 met inclusion criteria, comprising 1305 patients. Five studies have reported patients with visceral crises or ≥ 3 sites of metastasis. The ORR for CDK4/6i plus ET versus CT was 41% vs. 38%, and the progression rate was 6% vs. 9%. The SMD for the ORR (Hedges-G) was 0.5 in favor of CDK4/6i (95%CI 0.18 – 0.82, p = 0.002, I 2 = 0.0). The SMD for DoR (Median difference) was 6.7 favoring CDK4/6 (95%CI 1.73 - 11.67, p = 0.18, I 2 = 42.38%). PFS (Hazard ratio) was -0.33 in favor of CDK4/6i (95%CI -0.5 – 0.16, p = 0.001, I 2 = 84.5%). Conclusions: In HR+/HER2- breast cancer, CDK4/6i plus ET demonstrated superior ORR and significantly prolonged PFS compared to CT. However, the DoR advantage was not meaningful, and substantial heterogeneity was observed in PFS outcomes.