Treatment with sacituzumab govitecan plus pembrolizumab significantly extended time to second progression and the interval to subsequent treatment compared to chemotherapy plus pembrolizumab in patients with PD-L1-positive metastatic triple-negative breast cancer, according to late-breaking research presented at the 2026 ASCO Annual Meeting.

Results from the ASCENT-04 study established sacituzumab govitecan plus pembrolizumab as an advantageous first-line treatment for patients with PD-L1-positive metastatic triple-negative breast cancer, demonstrating a statistically significant progression-free survival (PFS) improvement compared to chemotherapy plus pembrolizumab. Data on overall survival were immature at the time of initial reporting.

In the ASCENT-04 study, patients initially assigned to chemotherapy could cross over to sacituzumab govitecan as a second-line treatment after presenting with independently confirmed progressive disease. The study also allowed patients to pursue other subsequent treatments for progressive breast cancer.

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and colleagues defined PFS2 as “the time from randomization to first documented progressive disease on next-line therapy per investigator assessment or death due to any cause, whichever occurred first.”

In the study, 221 patients were randomly assigned to sacituzumab govitecan plus pembrolizumab and 222 patients were randomly assigned to chemotherapy plus pembrolizumab. The median follow-up for OS was 14 months.

At the time of reporting, 43% of patients assigned to sacituzumab govitecan continued receiving their initial therapy, as did 23% of patients assigned to chemotherapy. In the sacituzumab govitecan arm, 69 patients sought subsequent treatments, including taxanes, platinum chemotherapy, and capecitabine.

In the chemotherapy arm, 119 patients sought subsequent treatment, the most frequent of which was sacituzumab govitecan. Other subsequent treatments included taxanes and capecitabine.

The median PFS2 was not reached for patients assigned to sacituzumab govitecan and was 21 months for patients assigned to chemotherapy.

PFS2 rates favored sacituzumab govitecan over chemotherapy at 12 months, 18 months, and 24 months.

Patients assigned to sacituzumab govitecan had a median time to subsequent treatment of 17.3 months, compared to 9.8 months for chemotherapy. The median time to second subsequent treatment was not reached in the sacituzumab govitecan arm; for chemotherapy, it was 21 months.

These findings “further support sacituzumab govitecan plus pembrolizumab as a potential new standard of care” for previously untreated patients with metastatic, PD-L1-positive triple-negative breast cancer, according to Tolaney and colleagues.

“Updated results from ASCENT-04 show that the benefit of sacituzumab govitecan plus pembrolizumab persisted beyond first disease progression with improvement in progression-free survival 2 and median time to first subsequent treatment, despite the crossover design of the trial and sacituzumab govitecan being the most commonly used second-line therapy among patients in the chemotherapy plus pembrolizumab arm. These results further support the use of sacituzumab govitecan and pembrolizumab in this patient population and are especially meaningful in a disease where improved outcomes are urgently needed.”

- Eleonora Teplinsky, MD, Head of Breast and Gynecologic Medical Oncology at Valley-Mount Sinai Comprehensive Cancer Care and an ASCO Expert in breast cancer

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Reference: https://www.asco.org/abstracts-presentations/259334

Disclosures: Some authors declared financial ties to drugmakers. See abstract for details. Funding for the study was provided by Gilead Sciences.

By Cameron Kelsall
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