Use of Metronomic Chemotherapy in Hormone Receptor‐Positive/ HER2 ‐Negative Metastatic Breast Cancer: A Retrospective Multicenter Study

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.