PATIENTS with unresectable, locally advanced or metastatic PD-L1-positive triple-negative breast cancer (TNBC) experienced longer progression-free survival when treated with sacituzumab govitecan and pembrolizumab, compared to the current standard of chemotherapy plus pembrolizumab, according to new findings presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
In the ASCENT-04/KEYNOTE-D19 phase 3 trial, 443 patients from 26 countries were randomized to receive either sacituzumab govitecan plus pembrolizumab (n=221) or chemotherapy plus pembrolizumab (n=222) as first-line treatment. After a median follow-up of 14 months, median progression-free survival (PFS) was 11.2 months in the sacituzumab govitecan group compared with 7.8 months in the chemotherapy group. This represented a 35% reduction in the risk of disease progression.
Sacituzumab govitecan is an antibody-drug conjugate that targets the Trop-2 protein expressed on tumor cells. While already approved in later-line settings for metastatic TNBC, this is the first phase 3 study to show improved disease control when used in combination with checkpoint inhibition as a first-line therapy.
The study also reported a longer median duration of response, 16.5 months versus 9.2 months, favoring the sacituzumab govitecan arm. Grade 3–4 adverse events were reported in both groups, with neutropenia being the most common (43% vs. 45%). Diarrhea occurred more frequently in the sacituzumab govitecan arm (10%) compared to anemia and thrombocytopenia in the chemotherapy arm (16% and 14%, respectively).
The researchers emphasized the clinical relevance of these findings, noting that a significant portion of patients with metastatic TNBC are unable to receive treatment beyond the first-line setting due to health decline or early mortality. Longer disease control at first-line could therefore address a key unmet need in this high-risk population.
Follow-up continues to determine whether this combination yields an overall survival advantage. Additional studies are underway in related breast cancer populations, including HER2-negative and hormone receptor-positive metastatic disease.
Reference:
Tolaney SM. ASCENT-04/KEYNOTE-D19 Trial: Sacituzumab Govitecan With Pembrolizumab in PD-L1-Positive TNBC. 2025. Available at: https://www.asco.org/about-asco/press-center/news-releases/sacituzumab-govitecan-helps-some-patients-pd-l1-positive. Last accessed: 2 June 2025.
