<b><i>Background:</i></b> Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients. <b><i>Objective:</i></b> The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane. <b><i>Methods:</i></b> Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3–4 drug-related adverse events were the outcomes assessed. <b><i>Results:</i></b> A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13–1.54, <i>p</i> < 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54–0.83, <i>p</i> < 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98–1.22, <i>p</i> = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy. <b><i>Conclusion:</i></b> Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.
Pre-specified interim analysis of the SAFE trial (NCT2236806): A 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab