First-Line Sacituzumab Govitecan After Endocrine Therapy Fails to Improve PFS in HR+/HER2-Negative Breast Cancer

Treatment with sacituzumab govitecan-hziy (Trodelvy) in the first line following endocrine therapy failed to improve progression-free survival (PFS) vs chemotherapy in patients with hormone receptor–positive, HER2-negative metastatic breast cancer, missing the primary end point of the phase 3 ASCENT-07 trial (NCT05840211).1

Although overall survival (OS) data were immature at the time of the primary analysis, an early trend favoring the sacituzumab govitecan arm over the chemotherapy arm was observed. Follow-up will continue to further assess this key secondary end point.

Of note, the safety profile of sacituzumab govitecan in ASCENT-07 was consistent with prior breast cancer studies evaluating the agent, and no new safety signals were identified.

“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,” Hope S. Rugo, MD, the principal investigator of ASCENT-07, as well as chief of the Division of Breast Oncology and director of Women’s Cancer Program at City of Hope in Duarte, California, stated in a news release. “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.”

What was the design of ASCENT-07?

ASCENT-07 was a global, open-label, randomized phase 3 trial evaluating the efficacy and safety of sacituzumab govitecan compared with physician’s choice of chemotherapy in patients with locally advanced, inoperable, or HR-positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+ and negative in situ hybridization) metastatic breast cancer who had received prior endocrine therapy and were candidates for cytotoxic chemotherapy.1,2

Specifically, they needed to have disease progression on at least 2 or more previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting; disease progression within 6 months of starting first-line endocrine therapy with or without a CDK4/6 inhibitor in the metastatic setting; or disease recurrence within the first 24 months of starting adjuvant endocrine therapy with a CDK 4/6 inhibitor and if the patient is no longer a candidate for additional endocrine therapy in the metastatic setting.2

A total of 654 patients were enrolled onto the study at 288 institutions across nearly 30 countries.1 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 treatment of physician’s choice, which included capecitabine, paclitaxel, or nab-paclitaxel (Abraxane). Treatment continued until disease progression or unacceptable toxicity, as confirmed by blinded independent central review (BICR).

The primary end point was PFS per RECIST 1.1 criteria as assessed by BICR. Key secondary end points included OS, objective response rate, quality of life, and safety.

What are the current indications for sacituzumab govitecan?

Sacituzumab govitecan is the only globally approved TROP-2–directed antibody-drug conjugate (ADC) to demonstrate a meaningful OS benefit in pretreated HR-positive, HER2-negative metastatic breast cancer and in second- and later-line metastatic triple-negative breast cancer (TNBC).1

The agent is recognized as a Category 1 preferred treatment for both approved indications in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. It is also the only ADC to hold a European Society for Medical Oncology–Magnitude of Clinical Benefit Scale rating of 5 for metastatic TNBC and 4 for HR-positive, HER2-negative metastatic breast cancer.

Sacituzumab govitecan is the first ADC to demonstrate statistically significant and clinically meaningful PFS improvements in the first-line metastatic TNBC setting, regardless of PD-L1 status, across both the phase 3 ASCENT-04 trial (NCT05382286) and phase 3 ASCENT-03 trial (NCT05382299). Notably, the ADC was given in combination with pembrolizumab (Keytruda) in ASCENT-04.

Ongoing evaluation of sacituzumab govitecan continues across multiple disease stages and tumor types, including the phase 3 ASCENT-05 trial (NCT05633654) in high-risk early-stage TNBC, as well as additional phase 3 studies in lung cancer and gynecologic malignancies.

“[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 [phase 3] TROPiCS-02 study [NCT03901339],” Dietmar Berger, MD, PhD, chief medical officer of Gilead Sciences, added in the news release. “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.”

References

1. Gilead provides update on phase 3 ASCENT-07 study. News release. Gilead. November 7, 2025. Accessed November 7, 2025. https://www.gilead.com/news/news-details/2025/gilead-provides-update-on-phase-3-ascent-07-study
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 7, 2025. https://www.clinicaltrials.gov/ct2/show/NCT05840211