Sacituzumab Govitecan Misses PFS End Point in Metastatic Breast Cancer

First-line post-endocrine therapy treatment with sacituzumab govitecan-hziy (Trodelvy) did not meet the primary end point of progression-free survival (PFS) compared with chemotherapy among patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer in the phase 3 ASCENT-07 trial (NCT05840211), according to a press release from the developer, Gilead.¹

Data for the key secondary end point of overall survival (OS) were immature at the time of the primary analysis. Investigators noted an early trend favoring the sacituzumab govitecan arm; the trial remains ongoing for further evaluation of OS.

Findings showed a safety profile that was comparable with prior reports of sacituzumab govitecan. Investigators reported no new safety signals in this breast cancer population.

“[HR-positive, HER2-negative] metastatic breast cancer is a highly heterogeneous disease, and this complexity makes it particularly challenging to manage, especially in patients whose disease has already progressed on multiple lines of endocrine therapy,” principal investigator Hope S. Rugo, MD, chief in the Division of Breast Oncology and director of the Women’s Cancer Program at City of Hope Comprehensive Cancer Center, stated in the press release.¹ “It will be critical that we continue to follow patients for [OS] to better understand the potential impact of sacituzumab govitecan long-term in this treatment setting.”

Investigators of the international, open-label phase 3 ASCENT-07 study assessed the safety and efficacy of sacituzumab govitecan vs chemotherapy among those with locally advanced, inoperable, or HR-positive and HER2-negative metastatic breast cancer following prior endocrine therapy. A total of 654 patients were randomly assigned 2:1 to receive sacituzumab govitecan at 10 mg/kg intravenously on days 1 and 8 of each 21-day cycle or investigator’s choice of capecitabine, paclitaxel, or nab-paclitaxel. Study treatment continued until disease progression verified by blinded independent central review (BICR) or unacceptable toxicity.

The trial’s primary end point was PFS per BICR based on RECIST v1.1 guidelines. Secondary end points included OS, objective response rate, quality of life, and safety.

Patients 18 years and older with documented evidence of HR-positive metastatic breast cancer, HER2 negativity, and eligibility for chemotherapy in the locally advanced or metastatic setting were eligible for enrollment on the trial.² Other eligibility criteria included having adequate organ function and an ECOG performance status of 0 or 1. Patients were permitted to enroll if they had received prior targeted therapies such as PARP inhibitors, PI3K inhibitors for PI3K-mutated disease, or mTOR inhibitors.

Those with progressive disease within 6 months of finishing neoadjuvant or adjuvant chemotherapy, locally advanced metastatic breast cancer of stage IIIc, or any prior treatment containing a chemotherapeutic agent directed towards topoisomerase I were ineligible for enrollment on the study. Patients were also unable to enroll if they had an active second malignancy, an active serious infection requiring antibiotics, active hepatitis B or hepatitis C virus, and a positive serum pregnancy test result or current breastfeeding status.

Sacituzumab govitecan is currently indicated for patients with unresectable, locally advanced or metastatic, triple-negative breast cancer following 2 or more prior lines of systemic therapy. Additionally, the agent is indicated for those with unresectable, locally advanced or metastatic, HR-positive, HER2-negative breast cancer following endocrine therapy and 2 or more lines of systemic therapy in the metastatic setting.

“[Sacituzumab govitecan] remains a standard of care for pretreated [HR-positive, HER2-negative] metastatic breast cancer based on the demonstrated [OS] results seen in the TROPiCS-02 study [NCT03901339]. We are deeply grateful to the patients, their families, advocates, and investigators who continue to contribute to this important research. We look forward to sharing the full data of ASCENT-07 at an upcoming medical conference,” Dietmar Berger, MD, PhD, chief medical officer at Gilead Sciences, concluded.¹

References

1. Gilead provides update on phase 3 ASCENT-07 study. News release. Gilead Sciences, Inc. November 7, 2025. Accessed November 10, 2025. https://tinyurl.com/mtpnt7vb
2. 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 November 10, 2025. https://tinyurl.com/mpr3tbzz