The antibody-drug conjugate sacituzumab govitecan (Trodelvy) did not improve progression-free survival among patients with endocrine-refractory hormone receptor (HR)+/HER2- advanced breast cancer when given before chemotherapy compared with standard of care, according to the phase 3 ASCENT-07 trial.

Among nearly 700 patients followed for 15 months, median progression-free survival was identical whether patients received sacituzumab or standard chemotherapy as the first treatment after endocrine therapy failure, researchers found.

Overall survival data are immature, but there was an early trend favoring sacituzumab, reported lead investigator Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York City.

“It will be critical that we continue to follow patients for overall survival to better understand the potential long-term impact of sacituzumab govitecan in this setting,” Jhaveri said during a press briefing.

She presented the results on December 10 at the San Antonio Breast Cancer Symposium (SABCS) 2025.

HR+/HER2- metastatic breast cancers are typically treated with endocrine therapy and CDK4/6 inhibitors, but treatment resistance is common, leaving patients with few options. Most move on to chemotherapy, which has shown marginal survival benefit and numerous toxicities.

There remains a “high unmet need” for additional options, Jhaveri said.

Sacituzumab, a TROP2-directed antibody-drug conjugate, has become the standard of care for HR+/HER2- advanced breast cancer after prior endocrine therapy and chemotherapy — based on the TROPiCS-02 trial, which showed clinically meaningful benefits for progression-free and overall survival.

Those results led Jhaveri and colleagues to investigate whether sacituzumab could be effective earlier in the treatment course — in patients who had received endocrine therapy but had not yet started chemotherapy.

The ASCENT-07 trial enrolled 690 patients with HR+/HER2- locally advanced, unresectable, or metastatic breast cancer whose disease had progressed after endocrine therapy and who were candidates for first chemotherapy.

Patients were randomly allocated (2:1) to receive sacituzumab govitecan or physician’s-choice chemotherapy, which included capecitabine, paclitaxel, or nab-paclitaxel.

The trial did not meet its primary endpoint of progression-free survival by blinded independent central review, Jhaveri reported. At a median follow-up of 15.4 months, median progression-free survival was 8.3 months in both treatment groups (hazard ratio [HR], 0.85; P = .130).

Median overall survival had not yet been reached in either group, though an early trend favoring sacituzumab was observed (HR, 0.72; nominal P = .029).

Objective response rates were similar but numerically higher in the sacituzumab group (37% vs 33%), while median duration of response was 12.1 months with sacituzumab and 9.3 months with chemotherapy.

As for safety, treatment-emergent adverse events of grade 3 or higher occurred more often with sacituzumab (72% vs 48%); the most common was neutropenia — occurring in 56% of patients receiving sacituzumab and 21% receiving chemotherapy.

Despite that, rates of dose reduction were similar between groups, and discontinuations due to adverse events were lower with sacituzumab (3% vs 7%).

Going forward, Jhaveri said her team will explore biomarker correlations to try to identify patient subsets who may derive benefit from earlier TROP-2-targeted therapy.

“Specifically, we will be looking into activity and efficacy by TROP-2 expression levels,” she noted.

Briefing moderator and SABCS program director Kate Lathrop, MD, also highlighted the need for biomarker data.

“There may be more of a biomarker-driven space here to select which patients could do better with an antibody-drug conjugate upfront,” Lathrop said. “So while the study did not meet its primary endpoint, it raises important questions about sequencing of antibody-drug conjugate therapy versus chemotherapy.”

Lathrop, of UT Health San Antonio, also noted that overall toxicity, excluding neutropenia, was “pretty even” between the trial groups, suggesting sacituzumab could still be an attractive option for some patients.

On the other hand, Lathrop said, given that sacituzumab requires multiple trips to the infusion clinic, oral agents such as capecitabine may be preferable to some patients in terms of quality of life.

The study was sponsored by Gilead Sciences. Jhaveri disclosed having relationships with Gilead Sciences, Novartis, Pfizer, and Genentech, among others. Lathrop disclosed having relationships with TeraSera Pharmaceuticals, Novartis, Pfizer, Eli Lilly and Company, and Encore Education.