Additional capecitabine use in early-stage triple negative breast cancer patients receiving standard chemotherapy: a new era? A meta-analysis of randomized controlled trials

BACKGROUND: The efficiency of capecitabine has been proven in early-stage triple negative breast cancer (eTNBC) with residue invasive tumor (non-pCR) after standard neoadjuvant chemotherapy (NACT). However, for those unselected eTNBC patients without screening from NACT (i.e., newly diagnosed eTNBC patients undergoing breast surgery followed by adjuvant systemic therapy), the value of capecitabine has still remains unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate whether additional capecitabine in eTNBC patients could improve clinical outcomes. METHODS: Seven RCTs (USO 01062, FinXX, GEICAM/2003, CREATE-X, CIBOMA/2004, CBCSG-010 and SYSUCC-001) were identified in online databases until December 2020 and included in the meta-analysis. We extracted the survival data including disease/relapse-free survival (DFS/RFS) and overall survival (OS), and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence intervals (95%CIs). RESULTS: A total of 3329 eTNBC patients were enrolled in this meta-analysis, with 1640 receiving standard neo−/adjuvant chemo-regimes alone, and the other 1689 receiving an additional capecitabine use, respectively. Both DFS and OS were significantly improved with the addition of capecitabine, and the benefits remained consistent in those unselected eTNBC patients without screening from NACT. Subgroup analysis further proved that this improvement in DFS was significant in both nodal negative and positive patients. Similar benefits are also found across menopausal status (both pre- and post-menopause). Regarding toxicity, the hand-foot syndrome and neutropenia are the most common capecitabine related adverse events, and are mostly tolerable. CONCLUSIONS: The present meta-analysis of RCTs demonstrates for the first time that adding capecitabine to standard chemo-regimens could improve both DFS and OS in unselected eTNBC patients, and this benefit remains consistent regardless of nodal status and menopausal status, which may lead eTNBC therapy into a new era.