Abstract
Introduction
Trophoblast cell surface antigen 2 (Trop-2), a transmembrane glycoprotein abundantly expressed in breast cancer tissues, has become a prominent target in precision cancer therapy, with Sacituzumab govitecan (SG) being the first antibody-drug conjugate (ADC) designed against it. Breast cancer, the most common malignancy in women, has a prognosis severely compromised by recurrence and metastasis. This meta-analysis of randomized controlled trials (RCTs) aims to systematically evaluate the clinical benefits and safety of SG in treating metastatic breast cancer (mBC). (
https://www.crd.york.ac.uk/PROSPERO/view/CRD420261347978
).
Methods
A systematic search was carried out in PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov, with a search period extending up to December 1, 2025, for RCTs examining the therapeutic efficacy and safety of SG for mBC. All statistical analyses were conducted using Review Manager (version 5.4), with pooled effect sizes computed using a fixed-effect or random-effects model depending on the degree of heterogeneity.
Results
A total of four phase III, multicenter, open-label RCTs were included in this systematic review. The experimental arm received sacituzumab govitecan (SG), and the control arm received chemotherapy. The efficacy analysis included 1,900 patients with metastatic breast cancer (mBC) (SG arm,
n
= 952; control arm,
n
= 948), and the safety analysis included 1,879 patients (SG arm,
n
= 966; control arm,
n
= 913). Compared with chemotherapy, SG significantly prolonged progression-free survival (PFS) (HR 0.58, 95% CI 0.46–0.72) and overall survival (OS) (HR 0.62, 95% CI 0.45–0.86). In addition, SG showed a trend toward higher objective response rate (ORR) and partial response (PR) rate, though neither difference was statistically significant; however, the complete response (CR) rate was significantly higher with SG (RR 1.94, 95% CI 1.11–3.38). The any-grade adverse events (AEs) with the highest reported incidence were neutropenia, followed by nausea, diarrhea, alopecia, anemia, and fatigue. Notably, treatment with SG was linked to a significantly elevated rate of grade ≥3 neutropenia (RR 1.24, 95% CI 1.06–1.46) and diarrhea (RR 8.46, 95% CI 1.48–48.51).
Conclusion
SG may provide clinical benefit and favorable effects on HRQoL in mBC; however, its more definitive clinical advantages and the magnitude of benefit still require further validation. In addition, SG is associated with toxicities including neutropenia and diarrhea, warranting appropriate prophylactic measures in clinical practice.
Systematic Review Registration
https://www.crd.york.ac.uk/PROSPERO/view/CRD420261347978
, PROSPERO CRD420261347978.