Dana-Farber Research Supports FDA Approval of New First-Line Therapy for Metastatic Triple-Negative Breast Cancer

The U.S. Food and Drug Administration (FDA) has approved the antibody-drug conjugate sacituzumab govitecan for first-line treatment of metastatic triple-negative breast cancer. This action is based on results from the ASCENT-03 & -04 global clinical trials, which Sara Tolaney, MD, MPH, chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, helped to lead. Both studies showed treatment with sacituzumab govitecan significantly improved progression-free survival either as monotherapy for patients who were ineligible for a checkpoint inhibitor or in combination with pembrolizumab for patients who were PD-L1 positive.

Triple-negative breast cancer is an aggressive and difficult to treat form of breast cancer that accounts for about 15 percent of all breast cancer cases. The five-year survival rate for patients with metastatic triple-negative breast cancer is just 12 percent. Sacituzumab govitecan is an antibody-drug conjugate designed to direct a potent chemotherapy drug into cancer cells by targeting a protein called TROP-2 that is found on triple-negative breast cancer cells. While the drug was previously approved as second line or later therapy for advanced triple-negative breast cancer, approximately half of the patients who receive the current standard first-line treatment for the disease are unable to receive a second line of therapy.

"As oncologists and investigators, we're always trying to move more effective therapies into earlier lines of treatment because we want patients to be able to have robust responses that potentially will translate into survival outcomes," says Tolaney. “This approval is heartening news for patients and the clinical community, and I believe offers a practice-changing, first-line treatment option for all patients across PD-L1 status.”

The global, open-label ASCENT-03 study enrolled 558 patients who were randomized to receive either sacituzumab govitecan or chemotherapy as a first-line treatment. Eligible patients had locally advanced or unresectable triple-negative breast cancer and were not candidates for immune checkpoint inhibitors. After a median follow-up of 13.2 months, patients treated with sacituzumab govitecan were more likely to survive longer without disease progression, with a median progression-free survival of 9.7 months compared to 6.9 months for patients treated with chemotherapy. Those who responded showed a median duration of response of 12.2 months, compared to 7.2 months for those patients who responded to chemotherapy. These data were presented at the European Society for Medical Oncology Congress 2025 and published simultaneously in the New England Journal of Medicine.

The global, open-label ASCENT-04 study enrolled 443 patients who were randomized to receive either sacituzumab govitecan plus pembrolizumab, an immune checkpoint inhibitor, or chemotherapy plus pembrolizumab. After a median follow-up of 14 months, patients who received the sacituzumab govitecan combination were more likely to survive longer without progression, with an 11.2 month median progression free survival compared to 7.8 months among those who received the chemotherapy combination. Nearly 60 percent of patients responded to the sacituzumab govitecan combination. Those who responded experienced durable responses with a median of 16.6 months compared to 9.2 months among those who responded to the chemotherapy combination. These results were presented at the 2025 ASCO Annual Meeting and published subsequently in the New England Journal of Medicine.

At ASCO 2026, additional analysis from these studies confirmed that moving sacituzumab govitecan to the first line of treatment confers long-term benefit compared to standard therapy, including continued benefit even after subsequent therapy. 

The ASCENT-03 and -04 trials were funded by Gilead Sciences, Inc.