Clinical Outcomes of Sacituzumab Govitecan in Breast Cancer: A Systematic Review, Meta-Analysis, and GRADE Assessment of Randomized Evidence.

OBJECTIVES: Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate delivering SN-38, has shown promising activity in advanced breast cancer. However, variability across trials and inclusion of nonrandomized data in prior meta-analyses limit the certainty of its efficacy and safety. This study aimed to evaluate the effectiveness and safety of SG using only randomized controlled trials (RCTs). METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed/MEDLINE, Embase, Scopus, and Cochrane Library were searched from June 2025 to April 2026. RCTs comparing SG with standard therapies in breast cancer patients were included. Outcomes included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events. Random-effects models were used to calculate pooled risk ratios (RR) and hazard ratios (HR) with 95% CIs. Risk of bias (RoB 2) and GRADE approaches were applied. RESULTS: Six RCTs (n=2508) were included. SG significantly improved ORR (RR=1.62; 95% CI: 1.11-2.37), OS (HR=0.68; 95% CI: 0.54-0.86), and PFS (HR=0.60; 95% CI: 0.51-0.72), although heterogeneity was moderate to high in some analyses. SG was associated with a higher risk of grade ≥3 adverse events (RR=1.12; 95% CI: 1.05-1.20), particularly diarrhea and neutropenia. Subgroup and sensitivity analyses confirmed the robustness of efficacy outcomes. CONCLUSIONS: SG provides significant improvements in survival and response outcomes in advanced breast cancer, with a manageable toxicity profile. These findings support its role as an effective treatment option, particularly in pretreated patients, while highlighting the need for further research to optimize its clinical use.