Sacituzumab Govitecan Plus Pembrolizumab Improves Progression-Free Survival in PD-L1–Positive Triple-Negative Breast Cancer

Clinical Summary: 

• Design/Population: The phase 3 ASCENT-04 trial compared first-line sacituzumab govitecan plus pembrolizumab with pembrolizumab plus chemotherapy in patients with PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer.
• Key Outcomes: Sacituzumab govitecan plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab plus chemotherapy and was associated with a numerically higher objective response rate and longer duration of response. Overall survival data were immature, and the safety profile was generally consistent between treatment groups.
• Clinical Relevance: These findings support combining a Trop-2–directed antibody-drug conjugate with PD-1 inhibition as a potential new first-line treatment strategy for PD-L1–positive advanced triple-negative breast cancer.

Results from the phase 3 ASCENT-04 trial demonstrated that first-line sacituzumab govitecan plus pembrolizumab significantly improved progression-free survival (PFS) compared with pembrolizumab plus chemotherapy in patients with PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer.

“Triple-negative breast cancer is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer,” stated Sara Tolaney, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors. 

In this open-label study, 443 patients were randomized 1:1 to receive either sacituzumab govitecan plus pembrolizumab (n = 221) or pembrolizumab plus physician's choice chemotherapy (n = 222). The primary end point was PFS, as assessed by blinded independent central review. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of response, and safety.

At the time of analysis, median PFS was 11.2 months with sacituzumab govitecan plus pembrolizumab compared with 7.8 months with pembrolizumab plus chemotherapy (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51 to 0.84; P < .001). The ORR was 60% and 53%, respectively, while median duration of response was 16.5 months and 9.2 months. OS data were immature.

Grade ≥3 adverse events occurred in 71% of patients receiving sacituzumab govitecan plus pembrolizumab and 70% of those receiving pembrolizumab plus chemotherapy. Adverse events led to treatment discontinuation in 12% and 31% of patients, respectively. Treatment-related deaths occurred in 3% of patients in each treatment arm.

“Sacituzumab govitecan plus pembrolizumab led to significantly longer [PFS] than chemotherapy plus pembrolizumab among patients with previously untreated, PD-L1–positive, advanced triple-negative breast cancer,” concluded Dr Tolaney et al. 

Source: 

Tolaney SM, De Evandro A, Kalinsky K, et al. Sacituzumab govitecan plus pembrolizumab for advanced triple-negative breast cancer. N Engl J Med. Published online: January 21, 2026. doi: 10.1056/NEJMoa2508959