Metronomic (mCHT) vs standard (sCHT) chemotherapy as first-line treatment in HR+/HER2- Metastatic Breast Cancer (MBC) patients following failure of endocrine treatments. The matched control VICTOR-15 study

Background: HR+/HER2- MBC patients often receive chemotherapy (CHT) following endocrine therapy (ET); however, treatment-related toxicities remain a significant limitation. Metronomic chemotherapy (mCHT) involves the administration of low-dose chemotherapeutic agents at regular intervals without extended breaks. The VICTOR-15 study is a retrospective, matched controlled study designed to compare mCHT with standard chemotherapy (sCHT) in HR+/HER2- metastatic breast cancer (MBC) patients after ET failure. Methods: We identified consecutive patients treated with mCHT or sCHT between 2015 and 2024. Each mCHT patient was matched with a variable number of women treated with sCHT based on multiple clinical and demographic factors. The primary endpoint was real world progression-free suvival (rwPFS). Secondary endpoints included Overall Survival (OS)), Overall Response Rate (ORR) and Clinical Benefit Rate (CBR). rwPFS and OS were estimated by a weighted Kaplan-Meyer to account for variable matching. Results: The final analysis included 27 patients treated with mCHT and 52 with sCHT patients after matching (min = 1, max = 5). The median age at treatment initiation was 60.9 years for the mCHT group and 60.3 years for the sCHT group. Prior CDK4/6 inhibitor therapy was reported in 51.9% of mCHT patients and 48.1% of sCHT patients. Visceral metastases were present in 70.4% of mCHT patients and 69.2% of sCHT patients. CBR and ORR were higher in the mCHT group compared to the sCHT group (CBR: 66.7% vs. 61.5%; ORR: 37.0% vs. 28.8%). Median rwPFS was 7.0 (95%CI=4.1-12.6) and 5.4 months (95%CI=3.9-7.0) for mCHT and sCHT. Median OS was 29.3 months (95%CI=22.4-44.9) for mCHT and15.3 months, (95%CI: 9.2-26.9) for sCHT. A higher proportion of patients in the sCHT group did not initiate a subsequent treatment compared to the mCHT group (23.1% vs 11.1%). Conclusion: mCHT demonstrated promising efficacy compared to sCHT following failure of ET±CDK 4/6i. This finding, combined with the generally favourable toxicity profile, supports the rationale for further randomized studies to better evaluate this therapeutic strategy.