Results from the global phase III ASCENT-04 clinical trial found that sacituzumab govitecan combined with pembrolizumab improved progression-free survival 2 (PFS2) in patients with PD-L1–positive metastatic triple-negative breast cancer when compared to chemotherapy with pembrolizumab. PFS2 is an emerging endpoint that is closely associated with overall survival. The research was presented at the 2026 ASCO Annual Meeting (Abstract LBA1000).
About the Study
ASCENT-04 included 443 patients from 26 countries who had not yet received treatment for either metastatic triple-negative breast cancer or locally advanced triple-negative breast cancer that could not be removed with surgery. All participants had PD-L1–positive tumors. The participants were randomly assigned to receive either sacituzumab govitecan with pembrolizumab (n = 221) or chemotherapy with pembrolizumab (n = 222). Patients in the chemotherapy group could receive second-line sacituzumab govitecan as a crossover treatment option.
Unlike the initial analysis for this study, this new analysis looked at the benefits of crossing over from one arm of the study to the other. The analysis also assessed outcomes based on PFS2, an indicator of long-term outcomes that closely mirrors overall survival. Researchers defined PFS2 as the length of time until either the cancer grew following second-line therapy or until death from any cause.
Key Findings
At a median follow-up of 14 months, 43% of people in the sacituzumab govitecan group remained on the initial treatment compared to 23% of participants in the chemotherapy group.
Of the 125 people in the sacituzumab govitecan group who had discontinued initial treatment, 69 received subsequent treatment. Of the 170 people in the chemotherapy group who discontinued treatment, 119 received subsequent treatment, 81% of whom received sacituzumab govitecan as their next treatment.
Overall, the median time to the first subsequent therapy was 17.3 months in the sacituzumab govitecan group vs 9.8 months in the chemotherapy group.
PFS2 was significantly improved in the sacituzumab govitecan group, with the median PFS2 not reached at the time of follow-up. By comparison, the median PFS2 was 21 months in the chemotherapy group. Both outcomes were considerably longer than the initial PFS outcomes, with sacituzumab govitecan plus pembrolizumab still clearly showing the most favorable results, especially over a longer period.
The median PFS2 rate was higher in the sacituzumab govitecan group at 1 year (80% vs 75.7% in the chemotherapy group), 18 months (71.9% vs 53%), and 2 years (63.7% vs 45.6%).
“In this analysis, PFS2 was improved in the sacituzumab govitecan plus pembrolizumab arm despite many patients in the control arm going on to receive sacituzumab govitecan in the second-line setting. This suggests that the benefit of giving pembrolizumab plus sacituzumab govitecan as first-line therapy over chemotherapy is sustained in the long term, further supporting this combination as a potential new standard of care,” said lead study author Kevin Kalinsky, MD, MS, FASCO, of the Winship Cancer Institute of Emory University in Atlanta, Georgia.
DISCLOSURE: This study was funded by Gilead Sciences Inc. For full disclosures of the study authors, visit coi.asco.org.
