Efficacy of sacituzumab govitecan, a Trop-2-directed antibody–drug conjugate, in metastatic triple-negative breast cancer

Summary Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease with limited treatment options. Antibody–drug conjugates (ADCs), particularly those targeting trophoblast cell-surface antigen 2 (Trop‑2), have emerged as an effective therapeutic strategy. Sacituzumab govitecan (SG), a Trop-2-directed ADC, has demonstrated clinical benefit across multiple disease settings in metastatic TNBC (mTNBC). In the phase III ASCENT trial, SG significantly improved progression-free survival (PFS: 4.8 vs. 1.7 months; HR: 0.41) and overall survival (OS: 11.8 vs. 6.9 months; HR: 0.51) compared with physician’s choice chemotherapy in patients with heavily pretreated mTNBC, with consistent benefit across Trop‑2 and HER2 expression subgroups. The phase III ASCENT-03 trial extended these findings to the first-line setting in patients with locally advanced or mTNBC who were not eligible for PD-1/PD-L1 inhibitor therapy. Sacituzumab govitecan significantly improved PFS versus chemotherapy (9.7 vs. 6.9 months; HR: 0.62), with more durable responses and a favorable safety profile. In ASCENT-04, SG combined with pembrolizumab significantly improved PFS compared with standard chemoimmunotherapy in previously untreated, PD-L1-positive TNBC (11.2 vs. 7.8 months; HR: 0.65), with higher response rates and prolonged duration of response. Together, results from the ASCENT program establish SG as a key therapeutic option across multiple lines of therapy in TNBC, supporting its role as both a first-line and later-line ADC-based treatment strategy.