Results from the global phase 3 ASCENT-04 clinical trial found that sacituzumab govitecan combined with pembrolizumab improved progression-free survival 2 (PFS2) in people with PD-L1-positive metastatic triple-negative breast cancer (mTNBC) 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 American Society of Clinical Oncology (ASCO) Annual Meeting, which took place May 29 to June 2 in Chicago. 

ASCENT-04 included 443 people from 26 countries who had not yet received treatment for either mTNBC or locally advanced TNBC 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 (221 people) or chemotherapy with pembrolizumab (222 people). The people 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 sacitzumab 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 of time.   
• 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 a large number of 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.

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

Source: ASCO

Watch the interview with Dr Hurvitz here