Sacituzumab Govitecan Misses PFS in First-Line HR+/HER2– Metastatic Breast Cancer

An update from the phase 3 ASCENT-07 trial (NCT05840211) evaluating sacituzumab govitecan-hziy (Trodelvy) against chemotherapy for first-line treatment of hormone receptor-positive (HR+), HER2-negative (HER2–) metastatic breast cancer revealed that the study did not meet its primary end point of progression-free survival (PFS).¹

Investigators are now looking to the trial’s key secondary end point of overall survival (OS), which was immature as of the update, but appears to show a positive trend favoring patients treated with sacituzumab govitecan over those treated with chemotherapy.

“HR+/HER2[–] 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,” said Hope S. Rugo, MD, chief of division of Breast Oncology and director of Women’s Cancer Program, City of Hope Comprehensive Cancer Center and ASCENT-07 principal investigator, in a news 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.”

Regarding safety, the safety profile remained in line with previous breast cancer studies of sacituzumab govitecan, with no new safety signals.

The sponsor intends to share full ASCENT-07 trial data at an upcoming medical conference.

About the ASCENT-07 Trial

The phase 3 ASCENT-07 trial is a randomized, open-label, global study assessing the efficacy and safety of first-line sacituzumab govitecan compared with standard-of-care chemotherapy in patients with locally advanced, unresectable, or HR+/HER2– metastatic breast cancer.² The primary end point is PFS; secondary end points include OS, objective response rate, quality of life and safety.

In the trial, an enrolled 654 patients have been randomized 2:1 to receive either 10 mg/kg of intravenous sacituzumab govitecan on days 1 and 8 of a 21-day cycle, or physician’s choice of chemotherapy, including paclitaxel, nab-paclitaxel, or capecitabine.

Sacituzumab Govitecan in Breast Cancer

Despite missing the primary end point in ASCENT-07, the Trop-2-directed antibody-drug conjugate has a successful track record in other treatment settings and indications and is indicated for 2 types of pre-treated metastatic breast cancer. The agent was initially approved in 2021 for treatment of patients with metastatic triple-negative breast cancer (mTNBC) who received 2 or more prior systemic therapies in the metastatic setting, supported by the phase 3 ASCENT study (NCT0257445). It also scored an approval 2 years later in 2023 for HR+/HER2– metastatic breast cancer treated with endocrine-based therapy and at least 2 additional systemic therapies, supported by the phase 3 TROPiCS-02 study (NCT03901339).

Other ongoing trials have generated evidence of PFS benefits by sacituzumab govitecan in the first-line setting. Most recently, results from the phase 3 ASCENT-03 trial (NCT05382299) shared at the 2025 European Society for Medical Oncology (ESMO) Congress revealed significant and clinically meaningful improvements in PFS by the agent compared with standard chemotherapy in patients with mTNBC, lowering the risk of disease progression or death by 38%.

Also in mTNBC, the agent combined with pembrolizumab (Keytruda) showed superior PFS over chemotherapy plus pembrolizumab in the phase 3 ASCENT-04 trial (NCT05382286), the results of which were presented earlier this year at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Here, a 35% risk reduction was achieved in the investigational treatment arm compared with the chemotherapy arm.

REFERENCES

1. Gilead provides update on phase 3 ASCENT-07 study. News release. Gilead Sciences. November 7, 2025. Accessed November 7, 2025. https://tinyurl.com/5n99m5fw

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/study/NCT05840211