Comparative efficacy and safety of sacituzumab govitecan versus chemotherapy in metastatic breast cancer: An updated meta-analysis and systematic review.

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Background: Sacituzumab Govitecan (SG) is a Trop-2–directed antibody–drug conjugate with demonstrated survival benefit in metastatic breast cancer. Estimating the magnitude of that benefit has been complicated by differences in trial populations, chemotherapy comparators, and the accumulation of new trial data. We performed an updated meta-analysis to pool estimates of PFS, OS, tumor response, and key adverse events across available comparative trials. Methods: We conducted a systematic review and meta-analysis per PRISMA guidelines, searching PubMed, Embase, Scopus, and the Cochrane Library from inception to 29 January 2026 for comparative trials of SG versus chemotherapy in metastatic breast cancer. Two reviewers independently screened studies and extracted data; disagreements were resolved by consensus. Hazard ratios (HRs) were pooled for PFS and OS; risk ratios (RRs) were used for dichotomous outcomes. Random-effects models were used as the primary analytic approach. Heterogeneity was assessed with I² and τ². Results: 4 studies (ASCENT [Bardia], TROPICS-02, Cortes 2025, Xu 2024) comprising 1,961 participants (984 SG, 977 control) were included. PFS, reported in three studies (ASCENT [Bardia], Cortes 2025, Xu 2024), favored SG (HR 0.54; 95% CI 0.43–0.69; I²=70.3%). OS, reported in three studies (ASCENT [Bardia], TROPICS-02, Xu 2024), was also improved (HR 0.64; 95% CI 0.49–0.83; I²=78.0%). Stable disease was significantly higher with SG across all four studies (RR 1.22; 95% CI 1.10–1.36; I²=0%), while partial response did not differ on random-effects analysis (RR 1.90; 95% CI 0.79–4.59; I²=91.0%). Grade 3 adverse events were more frequent with SG (4 studies; 966 vs 913 participants; RR 1.19; 95% CI 1.08–1.30; I²=46.9%). All-grade neutropenia (3 studies; 801 vs 749 participants) was numerically higher but not statistically significant (RR 1.26; 95% CI 0.98–1.62; I²=90.4%), and febrile neutropenia (2 studies; 526 vs 473 participants) did not differ significantly (RR 1.64; 95% CI 0.77–3.52; I²=33.8%). Treatment discontinuation due to adverse events was similar across both treatment discontinuation definitions examined (3 studies: RR 1.04; 95% CI 0.60–1.81; I²=0%; 2 studies: RR 0.66; 95% CI 0.14–3.01; I²=89.0%). Conclusions: SG improved PFS and OS versus chemotherapy in metastatic breast cancer and increased stable disease rates, with a modest increase in grade 3 events. Neutropenia signals were elevated but inconsistent across studies, and discontinuation rates did not differ significantly. The survival benefit is clinically meaningful; the hematologic toxicity profile and substantial heterogeneity across outcomes warrant attention in individual treatment decisions.