Results from an international phase III clinical trial show that treatment with sacituzumab govitecan-hziy and pembrolizumab helps patients with unresectable, locally advanced or metastatic PD-L1–positive triple-negative breast cancer live longer without disease progression compared with chemotherapy and pembrolizumab. The research will be presented at the 2025 ASCO Annual Meeting (Abstract LBA109).
About the Study
“A significant portion of patients with metastatic triple-negative breast cancer do not receive treatment beyond the first-line setting for various reasons, including a decline in their health or death, demonstrating an unmet need for first-line treatment options,” said lead study author Sara M. Tolaney, MD, MPH, Chief of the Division of Breast Oncology, Dana-Farber Cancer Institute in Boston, Massachusetts.
The ASCENT-04/KEYNOTE-D19 clinical trial was designed to study the use of the antibody-drug conjugate sacituzumab govitecan in combination with pembrolizumab as a first-line treatment for patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer. Sacituzumab govitecan is an antibody-drug conjugate. This type of targeted therapy pairs an antibody with an anticancer drug. The antibody carries the drug to a specific protein found on cancer cells. Sacitizumab govitecan targets a protein called Trop-2, which is found on tumor cells.
The trial enrolled 443 patients from 26 countries. The demographics of the participants were balanced between the two treatment arms and consistent with the characteristics of people diagnosed with metastatic triple-negative breast cancer. Patients were randomly assigned to receive either sacituzumab govitecan and pembrolizumab (n = 221) or chemotherapy and pembrolizumab (n = 222). Both treatments were given until disease progression or until the treatment needed to be stopped due to adverse effects.
Key Findings
After a median follow-up of 14 months, patients treated with sacituzumab govitecan and pembrolizumab had a progression-free survival of 11.2 months vs 7.8 months in the chemotherapy and pembrolizumab arm. Patients treated with sacituzumab govitecan and pembrolizumab had a 35% lower risk of disease progression compared with patients treated with chemotherapy and pembrolizumab.
Median duration of response was 16.5 months for the sacituzumab govitecan and pembrolizumab arm vs 9.2 months for the chemotherapy and pembrolizumab arm.
The most frequent grade 3 and 4 adverse events in the sacituzumab govitecan and pembrolizumab arm were neutropenia (43%) and diarrhea (10%). In the chemotherapy and pembrolizumab arm, the most frequent grade 3 and 4 adverse events were neutropenia (45%), anemia (16%), and thrombocytopenia (14%).
Significance and Next Steps
“This study shows that sacituzumab govitecan, when combined with pembrolizumab as an initial treatment for patients with metastatic triple-negative breast cancer, delivers superior disease control and fewer side effects compared to chemotherapy plus pembrolizumab. These findings build on the proven efficacy of sacituzumab govitecan alone later in treatment, and sacituzumab govitecan plus pembrolizumab will likely become a new front-line standard of care in this setting,” said Jane Lowe Meisel, MD, FASCO, Co-Director, Breast Medical Oncology, at the Winship Cancer Institute of Emory University School of Medicine, and an ASCO expert in breast cancer.
Researchers will continue to follow these patients to better understand if there is an overall survival benefit for patients treated with sacituzumab govitecan and pembrolizumab compared to the control group. This drug combination is also being studied in patients with human epidermal growth factor receptor (HER2)-negative metastatic breast cancer, early-stage triple-negative breast cancer, and hormone receptor–positive/HER2-negative metastatic breast cancer after hormone therapy.
Disclosure: The ASCENT-04/KEYNOTE-D19 study was funded by Gilead Sciences. For full disclosures of the study authors, visit coi.asco.org.
