Sacituzumab govitecan (TROP2 ADC) trends toward longer PFS vs chemo in HER2 IHC0 HR+/HER2− mBC (ASCENT-07 subgroup)

Sacituzumab govitecan (SG; a TROP2-directed antibody–drug conjugate delivering SN-38) was compared with chemotherapy treatment of physician’s choice (TPC: capecitabine, paclitaxel, or nab-paclitaxel) in the Phase 3 ASCENT-07 trial (NCT05840211) in HR+/HER2− locally advanced unresectable or metastatic breast cancer eligible for first chemotherapy after prior endocrine therapy. In the HER2 IHC0 subgroup (n=292; SG n=192 vs TPC n=100; 92%/91% prior ET+CDK4/6i; 88%/86% visceral disease), median PFS was 9.2 vs 8.1 months by BICR (HR 0.75, nominal p=0.060) and 8.5 vs 6.1 months by investigator (HR 0.66, nominal p=0.0024); ORR was essentially the same (41% vs 40%) but median DOR was longer with SG (10.8 vs 8.3 months). Grade ≥3 TEAEs were higher with SG (73% vs 46%) driven by neutropenia (54% vs 21%), yet discontinuations were lower (2% vs 7%); OS was immature (28% maturity) with a non-significant early trend (HR 0.68, nominal p=0.082; SG median OS not reached vs 20.2 months).