Trodelvy Misses Primary Endpoint in ASCENT-07 Breast Cancer Trial

In the phase 3 ASCENT-07 trial, Trodelvy (sacituzumab govitecan-hziy) given as the first treatment after endocrine therapy did not improve progression-free survival compared with standard chemotherapy in patients with hormone receptor–positive (HR-positive), HER2-negative metastatic breast cancer, according to a news release from Gilead Sciences, Inc.

The phase 3 study compared Trodelvy to physician’s choice chemotherapy in 654 patients across approximately 30 countries. The primary end point of the trial, progression-free survival, was not met. Despite this, an early trend was observed favoring Trodelvy in overall survival, a key secondary end point, which remains immature at the time of primary analysis. The ASCENT-07 study will continue to monitor overall survival to better understand the long-term impact of Trodelvy in this patient population.

Dr. Hope S. Rugo, the ASCENT-07 principal investigator and chief of the Division of Breast Oncology at City of Hope Comprehensive Cancer Center, emphasized the complexity of HR-positive, HER2-negative metastatic breast cancer, particularly in patients whose disease has progressed after multiple lines of endocrine therapy.

“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,” she explained. “It will be critical that we continue to follow patients for overall survival to better understand the potential impact of Trodelvy long-term in this treatment setting.”

The safety profile in ASCENT-07 was consistent with prior Trodelvy studies, and no new safety concerns were identified in this patient population.

Trodelvy Remains a Standard of Care for Pre-Treated HR-Positive, HER2-Negative Breast Cancer

Trodelvy is currently the only Trop-2-directed antibody-drug conjugate (ADC) approved globally to show meaningful overall survival benefits in both pre-treated HR-positive, HER2-negative metastatic breast cancer and second-line or later metastatic triple-negative breast cancer. It is recognized as a Category 1 preferred treatment for both approved indications according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology, the news release explained. Additionally, it carries a European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) rating of 5 for metastatic triple-negative breast cancer and 4 for HR-positive, HER2-negative metastatic breast cancer.

Overall, this means that the treatment is strongly recommended in treatment guidelines and has received high clinical benefit ratings in both the U.S. and Europe for breast cancer.

Trodelvy is a first-in-class ADC designed to target Trop-2, a protein expressed in over 90% of breast and lung cancers, and to deliver a topoisomerase I inhibitor payload (SN-38) directly to tumor cells and the surrounding microenvironment. This mechanism allows for targeted activity while minimizing exposure to healthy tissue.

The news release emphasized that Gilead will continue to study Trodelvy in multiple tumor types and disease stages, including ongoing phase 3 trials in high-risk early-stage triple-negative breast cancer and studies exploring its potential in lung and gynecologic cancers. The use of Trodelvy as a first treatment after endocrine therapy in HR-positive, HER2-negative metastatic breast cancer remains investigational, and safety and efficacy in this setting have not yet been established.

“Trodelvy remains a standard of care for pre-treated HR-positive/HER2-negative metastatic breast cancer based on the demonstrated overall survival results seen in [previous trials],” said Dr. Dietmar Berger, chief medical officer of Gilead Sciences. “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.”

Understanding HR-Positive, HER2-Negative Metastatic Breast Cancer and Treatment Options

HR-positive, HER2-negative metastatic breast cancer is the most common breast cancer subtype, representing approximately 70% of all cases globally, with around 400,000 diagnoses each year. While endocrine therapies can extend survival, nearly all patients with metastatic disease eventually progress and require chemotherapy. Standard chemotherapy is associated with limited clinical outcomes and higher rates of resistance, highlighting the need for effective and better-tolerated treatment options earlier in care.

The ASCENT-07 study enrolled patients with locally advanced, inoperable, or metastatic HR-positive, HER2-negative breast cancer who had received prior endocrine therapy and were candidates for cytotoxic chemotherapy.

Trodelvy has also treated over 60,000 cancer patients globally over the past five years, showing generally consistent clinical and real-world outcomes, the news release continued. Its established safety profile includes risks of neutropenia and diarrhea, which require monitoring and management, as detailed in the prescribing information.

Reference

1. “Gilead Provides Update on Phase 3 ASCENT-07 Study,” by Gilead Sciences, Inc. News release; Nov. 7, 2025.

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