Use of Metronomic Chemotherapy in Hormone Receptor‐Positive/HER2‐Negative Metastatic Breast Cancer: A Retrospective Multicenter Study
Abstract
ABSTRACT Purpose The optimal chemotherapy strategy after progression on cyclin‐dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor‐positive/human epidermal growth factor receptor 2‐negative (HR+/HER2−) metastatic breast cancer remains a matter of controversy. This study evaluated the efficacy of metronomic chemotherapy compared with other post‐CDK4/6i treatment strategies in a real‐world setting. Patients and Methods This retrospective multicenter study included patients with HR+/HER2− metastatic breast cancer progressing on CDK4/6i plus endocrine therapy and subsequently treated with systemic therapy. Progression‐free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety. Propensity score matching (1:2) was performed to reduce selection bias. Results A total of 177 patients were included, of whom 52 (29.4%) received metronomic chemotherapy. Among treatment strategies, metronomic chemotherapy achieved the longest median PFS (9 months; 95% CI: 5.46–12.53; p = 0.003). In multivariable analysis, metronomic chemotherapy was independently associated with prolonged PFS (HR 0.46, 95% CI: 0.30–0.69; p < 0.001). Median OS did not significantly differ across treatment groups. ORR was 48.0%, and CBR was 60.0% with metronomic chemotherapy. After propensity score matching, metronomic chemotherapy maintained a significant association with improved PFS (HR 0.49, 95% CI: 0.31–0.78; p = 0.003). Toxicities were predominantly Grade 1–2, with no severe adverse events reported in the metronomic cohort. Conclusion In this real‐world study, metronomic chemotherapy was associated with improved disease control and a favorable safety profile in patients with HR+/HER2− metastatic breast cancer progressing after CDK4/6i‐based therapy. Trial Registration Protocol Number 0037558/23