Efficacy and safety of adjuvant capecitabine and pembrolizumab in early-stage triple-negative breast cancer after standard neo-/adjuvant chemotherapy: A meta-analysis of phase III studies

Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high recurrence rates and poor prognosis. Capecitabine and pembrolizumab are emerging therapies aimed at improving survival outcomes in early-stage TNBC. This meta-analysis compares the efficacy of capecitabine and pembrolizumab in improving disease-free survival (DFS) and overall survival (OS) in early-stage TNBC. Methods: A systematic literature search identified four major randomized controlled trials (RCTs): CREATE-X, GEICAM, KEYNOTE-522, and SYSUCC-001. These studies investigated the efficacy of capecitabine and pembrolizumab in combination with chemotherapy in early-stage TNBC patients. Data on DFS and OS were pooled using a random-effects model, and heterogeneity was assessed using the I2 statistic. Results: The pooled analysis included 3133 participants across four trials. For OS, pembrolizumab demonstrated a significant benefit with a hazard ratio (HR) of 0.66 (95% CI: 0.64–0.79), indicating a 34% reduction in the risk of death. Capecitabine showed mixed results across studies, with a pooled HR of 0.75 (95% CI: 0.55–1.03). The pooled HR across these studies, calculated using a random-effects model, was found to be 0.69 (95% CI: 0.64 to 0.79). For DFS, pembrolizumab provided a consistent benefit (HR: 0.63, 95% CI: 0.43–0.93), while capecitabine resulted in a significant reduction in recurrence risk (HR: 0.67, 95% CI: 0.52–0.88). Conclusion: This meta-analysis demonstrates that pembrolizumab significantly improves survival outcomes in early-stage TNBC. Capecitabine also provides benefit, especially in DFS, but its impact on OS concerns residual disease. Further studies should explore optimal treatment regimens and combinations, as well as long-term survival data. © The Author(s) 2026