BACKGROUNDImmune checkpoint inhibitors combined with chemotherapy (ICI-chemo) and anti-angiogenesis therapy combined with chemotherapy (anti-angio-chemo) have demonstrated superiority over traditional chemotherapy in patients with advanced triple-negative breast cancer (TNBC). However, due to the absence of a direct comparison between ICI-chemo and anti-angio-chemo, it remains unclear which treatment is superior.OBJECTIVEThis study aimed to investigate the efficacy and safety of ICI-chemo or anti-angio-chemo for advanced TNBC at Sun Yat-sen University Cancer Center.METHODSA retrospective analysis was conducted on the medical records of advanced TNBC patients who received ICI-chemo or anti-angio-chemo treatment between January 2017 and March 2023. Survival outcomes and safety profiles were evaluated.RESULTSA total of 178 patients were enrolled, including 101 who received ICI-chemo and 77 who received anti-angio-chemo. The median follow-up time was 19.93 months [95 % confidence interval (CI): 17.05-22.81]. There was no significant difference in patient outcomes, including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) between the two treatment regimens in the overall population. However, ICI-chemo demonstrated clinical survival benefits, with significant improvements in PFS and OS [hazard ratio (HR) = 0. 546, P = 0.048; HR = 0.313, P = 0.032] in patients receiving first-line treatment. The median PFS (mPFS) for the ICI-chemo and anti-angio-chemo cohorts was 9.37 and 6.03 months, respectively. Univariate and multivariate analyses showed that ICI-chemo independently achieved favorable PFS. No statistically significant difference was observed in PFS or OS between patients who received second-line or later ICI-chemo or anti-angio-chemo. The mPFS was 4.83 and 5.03 months, respectively. The toxicity profiles of adverse events were similar across two cohorts.CONCLUSIONAmong patients with advanced TNBC, ICI-chemo is associated with potentially longer survival compared to anti-angio-chemo as first-line treatment. Given their efficacy and better cost-effectiveness, these two treatment regimens may be considered potentially effective options for second-line therapy and beyond.