Dr Jones on the Implications of Data from ASCENT-04 for First-Line PD-L1+ TNBC Management

"This study was [aiming to determine] what our best drug is for… these patients who are PD-L1–positive, and [the results] showed that it's sacituzumab govitecan plus immunotherapy."

Jade E. Jones, MD, a medical oncologist at Winship Cancer Institute and assistant professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, discussed the clinical implications of primary findings from the phase 3 ASCENT-04/KEYNOTE-D19 study (NCT05382286) for treatment selection in metastatic triple-negative breast cancer (TNBC), as discussed during the Bridging the Gaps in Breast Cancer concensus meeting.

Data from ASCENT-04/KEYNOTE-D19 were presented at the 2025 ASCO Annual Meeting, and demonstrated that sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) compared with chemotherapy plus pembrolizumab in patients with PD-L1–positive, advanced or metastatic TNBC. As of the March 3, 2025, data cutoff, the sacituzumab govitecan combination (n = 221) yielded a median PFS of 11.2 months (95% CI, 9.3-16.7) vs 7.8 months (95% CI, 7.3-9.3) with chemotherapy plus pembrolizumab (n = 222), corresponding to a 35% reduction in the risk of disease progression or death (HR, 0.65; 95% CI, 0.51-0.84; P < .001).

Jones emphasized the importance of identifying the most effective first-line therapy for this population. She noted that metastatic TNBC is associated with poor prognosis and limited treatment windows, as nearly half of patients may not be able to proceed to subsequent lines of therapy before experiencing death. Accordingly, these patients should receive the most impactful regimen upfront, so as to improve their chances of survival and quality of life.

The ASCENT-04/KEYNOTE-D19 trial specifically addressed whether sacituzumab govitecan plus pembrolizumab could provide greater benefit than the prior standard of chemotherapy plus pembrolizumab in PD-L1–positive disease, she detailed. The results support the sacituzumab-based combination as the preferred option in this biomarker-defined patient population, based on its efficacy in prolonging PFS and the potential to maximize early treatment impact, Jones concluded.