Sacituzumab Govitecan Shows Early Signs of Benefit in HR+/HER2− Metastatic Breast Cancer

Sacituzumab govitecan (SG; Trodelvy, Gilead Sciences) yielded favorable overall survival (OS) trends in patients with hormone receptor–positive, HER2-negative (HR+/HER2−) metastatic breast cancer, according to primary results from the phase 3 ASCENT-07 trial (NCT05840211).¹ The data were presented at the 2025 San Antonio Breast Cancer Symposium.

ASCENT-07 Design and Methods

In ASCENT-07, 690 adults with HR+/HER2−, locally advanced unresectable or metastatic breast cancer were randomly assigned to receive SG 10 mg/kg intravenously or chemotherapy of physician’s choice (TPC; capecitabine, nab-paclitaxel, or paclitaxel). Randomization was stratified by prior CDK4/6 inhibitor use, HER2 immunohistochemistry status, and geographic region.²

The primary end point was progression-free survival (PFS) as assessed by blinded independent central review (BICR) per RECIST v1.1. Key secondary end points included OS, objective response rate (ORR), and quality of life. Other secondary outcomes included duration of response (DOR) and safety assessments.²

ASCENT-07 Primary Results

Of the participants, 456 received SG and 234 received TPC. Median age was about 57 years, and the majority had previously received CDK4/6 inhibitors for metastatic disease (SG, 93%; TPC, 92%).²

At a median follow-up of 15.4 months, SG did not show a statistically significant improvement in PFS by BICR compared with TPC (hazard ratio [HR], 0.85; 95% CI, 0.69–1.05; P = 0.130). However, PFS by investigator assessment showed a numerical improvement with SG (HR, 0.78; 95% CI, 0.64–0.93; nominal P = 0.008).²

OS data were immature at primary analysis (27% maturity), but an early trend favored SG (HR, 0.72; 95% CI, 0.54–0.97; nominal P = 0.029). ORR by BICR was comparable between SG and TPC (37% vs 33%), while median DOR was longer with SG (12.1 vs 9.3 months).²

The most common grade 3 or higher treatment-emergent adverse event (AE) was neutropenia (SG, 56%; TPC, 21%). Despite higher rates of severe AEs with SG, dose reductions were similar between groups, and fewer participants discontinued treatment with SG compared with TPC.²

Conclusions

ASCENT-07 did not meet its primary end point of PFS by BICR in HR+/HER2−, locally advanced unresectable or metastatic breast cancer patients receiving first chemotherapy after prior endocrine therapy. No new safety concerns were identified. An early trend toward OS improvement with SG was observed, and further follow-up will continue to assess survival outcomes.

These results suggest that although SG may not significantly extend PFS in this setting, its tolerability profile and potential OS benefit warrant continued investigation.

REFERENECES

1. Study of sacituzumab govitecan versus treatment of physician's choice in patients with hormone receptor-positive/​human epidermal growth factor receptor 2 negative (HR+/​HER2-) metastatic breast cancer who have received endocrine therapy (ASCENT-07). ClinicalTrials.gov. Updated October 3, 2025. Accessed December 23, 2025. https://clinicaltrials.gov/study/NCT05840211

2. Jhaveri K, Park Y, Barrios C, et al. 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. Presented at: SABCS 2025. December 9-12, 2025. San Antonio, TX. Abstract GS1-09