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Updated: Jan 23, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer
Sara M Tolaney1, Evandro de Azambuja2, Kevin Kalinsky3
1Dana-Farber Cancer Institute, Harvard Medical School, Boston.
Background:
Triple-negative breast cancer is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, programmed death ligand 1 (PD-L1)-positive, locally advanced unresectable or metastatic triple-negative breast cancer.
Methods:
In this phase 3, open-label, international trial, we randomly assigned patients in a 1:1 ratio to receive sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included overall survival, objective response (complete or partial response) and duration of response as assessed by blinded independent central review, and safety.
Results:
A total of 443 patients were randomly assigned to receive sacituzumab govitecan plus pembrolizumab (221 patients) or chemotherapy plus pembrolizumab (222 patients). The median progression-free survival was 11.2 months (95% confidence interval [CI], 9.3 to 16.7) with sacituzumab govitecan plus pembrolizumab and 7.8 months (95% CI, 7.3 to 9.3) with chemotherapy plus pembrolizumab (hazard ratio for disease progression or death, 0.65; 95% CI, 0.51 to 0.84; two-sided P<0.001). Data for overall survival were immature. The percentage of patients with an objective response was 60% (95% CI, 53 to 66) with sacituzumab govitecan plus pembrolizumab and 53% (95% CI, 46 to 60) with chemotherapy plus pembrolizumab; among patients with a response, the median duration of response was 16.5 months (95% CI, 12.7 to 19.5) and 9.2 months (95% CI, 7.6 to 11.3), respectively. Adverse events of grade 3 or higher occurred in 71% of the patients receiving sacituzumab govitecan plus pembrolizumab and in 70% of those receiving chemotherapy plus pembrolizumab; the incidence of treatment discontinuation due to adverse events was 12% and 31%, respectively. Adverse events leading to death occurred in 3% of the patients in each group.
Conclusions:
Sacituzumab govitecan plus pembrolizumab led to significantly longer progression-free survival than chemotherapy plus pembrolizumab among patients with previously untreated, PD-L1-positive, advanced triple-negative breast cancer. (Funded by Gilead Sciences; ASCENT-04/KEYNOTE-D19 ClinicalTrials.gov number, NCT05382286.).
Insights
Sacituzumab govitecan combined with pembrolizumab significantly improved progression-free survival for advanced triple-negative breast cancer. This combination therapy offers a new option for patients with PD-L1 positive disease.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
- Unmet need exists for improved outcomes in advanced, PD-L1-positive, unresectable or metastatic TNBC.
- Programmed death ligand 1 (PD-L1) positivity is a key biomarker in TNBC treatment selection.
Purpose of the Study:
- To evaluate the efficacy and safety of sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab.
- To determine the impact of this combination on progression-free survival (PFS) in previously untreated advanced TNBC.
- To assess secondary endpoints including overall survival, objective response rate, duration of response, and safety.
Main Methods:
- Phase 3, open-label, international randomized trial.
- 1:1 randomization to sacituzumab govitecan + pembrolizumab or chemotherapy + pembrolizumab.
- Primary endpoint: PFS by blinded independent central review; secondary endpoints: OS, ORR, DOR, safety.
Main Results:
- Sacituzumab govitecan + pembrolizumab showed significantly longer median PFS (11.2 months) vs chemotherapy + pembrolizumab (7.8 months).
- Objective response rate was 60% for sacituzumab govitecan + pembrolizumab vs 53% for chemotherapy + pembrolizumab.
- Grade 3+ adverse events were similar (71% vs 70%), but treatment discontinuation due to AEs was lower with sacituzumab govitecan (12% vs 31%).
Conclusions:
- Sacituzumab govitecan plus pembrolizumab demonstrated superior PFS compared to chemotherapy plus pembrolizumab in first-line advanced TNBC.
- This combination represents a significant advancement for patients with PD-L1-positive advanced triple-negative breast cancer.
- The study was funded by Gilead Sciences and registered as ASCENT-04/KEYNOTE-D19 (NCT05382286).
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