Abstract
BACKGROUND: As metastasis drives the majority of breast cancer-related deaths, improving outcomes for metastatic breast cancer (MBC) remains a crucial challenge. Observational studies using target trial emulation are increasingly applied to estimate treatment effects, providing insights when randomized trials are not viable. OBJECTIVES: To estimate the effect of progression-free survival (PFS) of metronomic chemotherapy of weekly paclitaxel plus cisplatin (DP) compared with treatment of the physician's choice (TPC) for MBC. DESIGN: This analysis was designed as a retrospective cohort study according to STROBE criteria. METHODS: This retrospective cohort study compared metronomic chemotherapy of weekly DP versus TPC in MBC. The DP regimen included paclitaxel (80 mg/m(2)) on days 1, 8, 15, 22 and cisplatin (25 mg/m(2)) on days 1, 8, 15 in a 28-day cycle. Women aged ⩾18 years with MBC treated with at least one prior therapy between April 2014 and January 2023 at Renji Hospital were included. Propensity score matching (1:3) adjusted for confounding. The matched cohort subsequently underwent emulation of a randomized target trial, including cloning, censoring and weighting. The primary endpoint was PFS. RESULTS: Among 313 matched patients (83 on DP, 230 on TPC), DP showed a median PFS of 13.5 months (95% CI 10.3-16.6) versus 7.9 months (95% CI: 6.7-9.1) for TPC (hazard ratio (HR) 0.77, 95% CI 0.60-0.99). Target trial emulation further improved PFS in the DP arm to 14.1 months (95% CI: 13.3-16.6) versus 8.3 months (95% CI: 8.0-8.6) for TPC (HR 0.59, 95% CI: 0.54-0.64). Subgroup analysis and sensitivity analyses confirmed result robustness. CONCLUSION: This study demonstrates that weekly metronomic DP chemotherapy reduces disease progression in MBC patients, particularly in first-line settings. These findings support its potential as a treatment option and warrant further study for broader application.