Abstract GS1-09: Sacituzumab govitecan vs chemotherapy as first therapy after endocrine therapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer: Primary results from ASCENT-07

Abstract Background: Patients with hormone receptor positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) refractory to endocrine therapy (ET) have poor prognosis with short progression-free survival (PFS), low overall survival (OS) rate, and limited treatment options. In the phase 3 TROPiCS-02 trial, sacituzumab govitecan (SG) significantly improved median PFS and OS vs chemotherapy in participants with HR+/HER2− mBC who had received prior chemotherapy. We report primary results from the randomized phase 3 ASCENT-07 study (NCT05840211) in adults with HR+/HER2−, locally advanced unresectable or mBC who have received prior ET and are candidates for first chemotherapy. Methods: Participants were randomized 2:1 to receive SG 10 mg/kg IV or chemotherapy treatment of physician’s choice (TPC; capecitabine, nab-paclitaxel, or paclitaxel). Randomization was stratified by duration of prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) use in the metastatic setting, HER2 IHC status, and geographic region. The primary endpoint was PFS by blinded independent central review (BICR) per RECIST v1.1. Key secondary endpoints were OS, objective response rate (ORR) by BICR, and quality of life; other secondary endpoints were PFS and ORR by investigator assessment, duration of response (DOR) by BICR and investigator assessment, and safety. Results: Of 690 participants randomized, 456 received SG and 234 received TPC. Median age was 57 years; 424 (93%) participants in the SG group and 215 (92%) in the TPC group received prior CDK4/6i for mBC. With median follow-up of 15.4 months, SG did not show statistically significant improvement in PFS by BICR vs TPC (hazard ratio [HR], 0.85; 95% CI, 0.69-1.05; P = 0.130). PFS by investigator assessment showed numerical improvement with SG versus TPC (HR, 0.78; 95% CI, 0.64-0.93; nominal P = 0.008). Although OS data were not mature at the primary analysis (maturity rate, 27%), an early trend in improvement favoring SG was observed (HR, 0.72; 95% CI, 0.54-0.97; nominal P = 0.029). ORR by BICR was similar with SG (37%) than with TPC (33%) and median DOR by BICR was longer (12.1 vs 9.3 months for SG and TPC, respectively). The most common grade ≥ 3 treatment-emergent adverse event (TEAE) in both treatment groups was neutropenia (SG: 56%; TPC: 21%). Despite higher proportion of participants experiencing grade ≥ 3 TEAEs with SG vs TPC, rates of dose reduction were similar and treatment discontinuation was lower with SG vs TPC (Table). Conclusions: The study did not meet the primary endpoint of PFS by BICR in participants with HR+/HER2−, locally advanced unresectable or mBC who have received prior ET and are candidates for first chemotherapy. No new safety concerns were identified. An early trend in improvement of OS was observed, and the study will continue to further assess OS. Citation Format: K. L. Jhaveri, Y. Park, C. Barrios, G. Curigliano, H. Iwata, J. Cortés, D. Loirat, T. Pascual, Z. Shao, C. Araneda, T. Yamashita, M. Tapia, P. Cinar, S. Lam, X. Ren, W. Verret, J. Kwan, K. Punie, H. S. Rugo. Sacituzumab govitecan vs chemotherapy as first therapy after endocrine therapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer: Primary results from ASCENT-07 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS1-09