Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: A Systematic Review with Meta-Analysis of Single-Arm Efficacy and Integration of Randomized and Real-World Evidence

Background/Objectives: Metastatic triple-negative breast cancer (mTNBC) carries a poor prognosis and limited treatment options. Sacituzumab govitecan (SG), an anti-Trop-2 antibody-drug conjugate, has shown activity in this setting, but a quantitative synthesis integrating randomized and real-world evidence-particularly in underrepresented subgroups-was lacking. We aimed to summarize the comparative benefit of SG, which derives from a single randomized trial, and to assess whether trial-level efficacy is consistent with the activity observed in routine practice. Methods: Following PRISMA 2020, we searched PubMed/MEDLINE and Web of Science (January 2017-April 2026) for trials and observational cohorts of SG monotherapy in mTNBC. Comparative effects were taken from randomized data; single-arm efficacy (objective response rate [ORR], clinical benefit rate [CBR], median progression-free [PFS], and overall survival [OS]) was pooled using random-effects models. Risk of bias was assessed with RoB 2 and ROBINS-I. The review was registered in the Open Science Framework. Results: Nine studies (1242 patients; 980 SG-treated) were included: one randomized trial (ASCENT), two single-arm trials, and six real-world cohorts. In ASCENT, SG improved PFS (hazard ratio [HR] 0.41, 95% CI 0.33-0.63) and OS (HR 0.51, 0.42-0.64). Pooled ORR was 31.1% (28.0-34.4), and CBR was 42.2% (37.7-46.8), with the median PFS being 4.8 months (4.4-5.3) and OS being 11.0 months (9.3-13.0); trial-derived and real-world estimates were concordant. The benefit persisted in older patients (HR 0.25) and Black women (HR 0.44) but not in those with brain metastases (HR 0.68, 0.38-1.23). Conclusions: SG shows clinically meaningful activity in mTNBC that is broadly consistent between controlled trials and routine practice. Comparative superiority over chemotherapy rests on a single randomized trial (ASCENT); the pooled single-arm estimates describe activity and its consistency rather than a comparative effect.

Description

Author Contributions: Conceptualization, M.P.-B. and M.M.-A.; methodology, M.P.-B., M.T.M.-L., J.P.-M. and I.V.; software, M.P.-B. and J.P.-M.; validation, M.P.-B., M.M.-A., M.T.M.-L., J.P.-M., M.E.L.- G., F.T.-A., A.M.P.-F., M.M.-P. and I.V.; formal analysis, M.P.-B. and M.T.M.-L.; investigation, M.P.-B., M.M.-A., M.T.M.-L., J.P.-M., M.E.L.-G., F.T.-A., A.M.P.-F., M.M.-P. and I.V.; data curation, M.P.-B., M.M.-A. and I.V.; writing—original draft preparation, M.P.-B., M.M.-A., M.T.M.-L., J.P.-M., M.E.L.-G., F.T.-A., A.M.P.-F., M.M.-P. and I.V.; writing—review and editing, M.P.-B., M.M.-A., M.T.M.-L., J.P.-M., M.E.L.-G., F.T.-A., A.M.P.-F., M.M.-P. and I.V.; supervision, M.P.-B. and M.T.M.-L. All authors have read and agreed to the published version of the manuscript.