Sacituzumab Govitecan Does Not Meet Statistical Significance in HR+/HER2– mBC

The primary end point of PFS was not statistically significant with sacituzumab govitecan vs chemotherapy as first-line treatment in HR+/HER2– metastatic breast cancer.

Updated results from the phase 3 ASCENT-07 study (NCT05840211) found that progression-free survival (PFS) was not statistically significant when first-line sacituzumab govitecan-hziy (Trodelvy) after endocrine therapy was used to treat patients with hormone-receptor–positive/HER2-negative breast cancer, compared with chemotherapy. These results were presented in a press briefing at the 2025 San Antonio Breast Cancer Symposium (SABCS).

The median PFS blinded independent central review (BICR) in the sacituzumab arm was 8.3 months (95% CI, 8.1-10.3) vs 8.3 months (95% CI, 6.9-10.0) in the chemotherapy arm (HR, 0.85; 95% CI, 0.69-1.05; P = .130). At 6 months, the PFS rate was 71% (95% CI, 66%-75%) vs 64% (95% CI, 57%-71%), while the 12-month rates were 40% (95% CI, 35%-45%) vs 37% (95% CI, 29%-44%), respectively.

The median PFS by investigator assessment was 8.4 months (95% CI, 8.2-9.7) in the sacituzumab arm vs 6.4 months (95% CI, 6.0-8.1) in the chemotherapy arm (HR, 0.78; 95% CI, 0.64-0.93; P = .008). The 6-month PFS rate was 69% (95% CI, 64%-73%) vs 58% (95% CI, 51%-64%), and the 12-month PFS rate was 36% (95% CI, 32%-41%) vs 30% (95% CI, 24%-36%) between both arms, respectively.

The overall survival (OS) in the primary analysis had a 27% maturity. The median OS was not reached (NR; 95 % CI, NR-NR) in the sacituzumab arm vs NR (19.7-NR) in the chemotherapy arm (HR, 0.72; 95% CI, 0.54-0.97; P = .029). Of note, 61% of patients in the chemotherapy group were given sacituzumab after treatment discontinuation. The investigators noted that while the data were not mature, an early trend was observed favoring sacituzumab over chemotherapy.

“The ASCENT-07 study in participants with hormone receptor-positive/HER2-negative metastatic breast cancer eligible for first [line] chemotherapy did not meet statistical significance for the primary end point of PFS by BICR,” lead study author Komal Jhaveri, MD, FACP, FASCO, section head of the Endocrine Therapy Research Program, clinical director of Early Drug Development Services, and the Patricia and James Cayns Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center, said during the presentation.

A total of 690 patients were randomly assigned 2:1 to receive either intravenous sactituzumab govitecan (n = 456) at 10 mg/kg on days 1, 8, and 21; in the chemotherapy arm (n = 234), the physician gave patients either capecitabine, paclitaxel, or nab-paclitaxel. The primary end point was PFS by BICR. Secondary end points included OS, overall response rate by BICR, and quality of life.

Patients were stratified by the duration of prior CDK4/6 inhibitors for metastatic breast cancer, HER2 immunohistochemistry, and geographic region. Patients were enrolled if they had locally advanced unresectable or metastatic hormone-receptor–positive/HER2-negative breast cancer including: no prior chemotherapy, measurable disease, and either progression on 2 or more lines of endocrine therapy with or without targeted therapy, progression less than 6 months from starting first-line endocrine therapy with or without CDK4/6 inhibitor, or recurrence less than 24 months from starting endocrine therapy plus a CDK4/6 inhibitor and may no longer be a candidate for additional endocrine therapy.

The data cutoff for the primary PFS analysis was September 15, 2025. At that time, there were 419 PFS events observed with a 61% maturity, and 187 OS events with a 27% maturity. Of note, the study had a 99% power to detect a PFS HR at a 2-sided significant level with a minimum durable difference HR of 0.815. The median duration of follow-up was 15.4 months.

In the sacituzumab arm, the median duration of treatment was 8.3 months (range, 0.0-22.1) vs 6.1 months (range, 0.3-21.1) in the chemotherapy arm. The median relative dose intensity was 86.2% (range, 33.1-135.5) vs 93.0% (range, 43.2-108.4).

Any treatment-emergent adverse effects (TEAEs) occurred in more than 99% of patients in the sacituzumab govitecan arm vs 97% in the chemotherapy arm, and grade 3 or higher TEAEs in 72% vs 48%. Treatment-emergent serious AEs were noted in 23% vs 15%. Additionally, TEAEs leading to discontinuation occurred in 3% vs 7%, dose interruption in 75% vs 46%, dose reduction in 39% vs 38%, and death in 2% vs 2%.

Treatment-related adverse effects (TRAEs) were noted in more than 99% of patients in the sacituzumab arm vs 93% in the chemotherapy arm, with grade 3 or higher TRAEs in 68% vs 37%. Treatment-related serious AEs occurred in 16% vs 5% of patients. Additionally, TRAEs leading to death occurred in 1% vs 1%.

“Sacituzumab govitecan remains a standard of care for hormone-receptor–positive/HER2-negative metastatic breast cancer after prior endocrine therapy and chemotherapy based on the phase 3 TROPiCS-02 study,” Jhaveri concluded.

Reference

Jhaveri K, Park YH, 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 the 2025 San Antonio Breast Cancer Symposium (SABCS); December 9-12, 2025. Abstract GS1-09.