Sacituzumab Govitecan Potential New Standard of Care for PD-L1 Blockade-Ineligible Patients With Metastatic Triple-Negative Breast Cancer
Key Clinical Takeaways
- Design/Population: The phase 3 ASCENT-03 trial was an open-label, randomized study evaluating sacituzumab govitecan versus standard chemotherapy in 558 patients with previously untreated metastatic triple-negative breast cancer (TNBC) ineligible for PD-L1 inhibitors. Patients were randomized 1:1 to receive sacituzumab govitecan 10 mg/kg on days 1 and 8 of each 21-day cycle or standard chemotherapy with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin.
- Key Outcomes: At a median follow-up of 13.2 months, sacituzumab govitecan significantly improved median progression-free survival to 9.7 months versus 6.9 months with chemotherapy (HR, 0.62; P < .0001). The median duration of response was 12.2 months with sacituzumab govitecan compared with 7.2 months for chemotherapy, and overall survival data were immature at the time of analysis
- Safety: Grade ≥3 treatment-emergent adverse events occurred in 66% of patients receiving sacituzumab govitecan and 62% receiving chemotherapy. Neutropenia and diarrhea were the most common events in the sacituzumab govitecan arm, while neutropenia and anemia were most frequent with chemotherapy.
- Clinical Relevance: Sacituzumab govitecan demonstrated a meaningful improvement in efficacy over standard chemotherapy for patients with metastatic TNBC unable to receive PD-L1 inhibitors. These findings support sacituzumab govitecan as a potential new standard of care in this patient population.
Results from the phase 3 ASCENT-03 trial show that sacituzumab govitecan significantly improved efficacy and safety compared with standard chemotherapy among previously untreated patients with metastatic triple-negative breast cancer (TNBC) unable to receive PD-L1 inhibitors.
These results were presented by Javier Cortés, MD, PhD, International Breast Cancer Centre, Barcelona, Spain, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In this open-label study, researchers enrolled 558 patients with locally advanced unresectable or metastatic TNBC who were either PD-L1–positive (combined positive score [CPS] < 10) or PD-L1–negative (CPS ≥ 10) and ineligible for PD-L1 blockade due to prior exposure or comorbidities. Patients were randomized on a 1-to-1 basis to receive either 10 mg/kg of sacituzumab govitecan on days 1 and 8 of each 21-day cycle (n = 279) or standard chemotherapy with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin (n = 279). The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS), objective response rate (ORR), duration of response, and safety.
At a median follow-up of 13.2 months, median PFS was 9.7 months in the sacituzumab govitecan arm and 6.9 months in the chemotherapy arm (hazard ratio [HR] 0.62; 95% confidence interval [CI], 0.50 to 0.78; P < .0001). Median ORR was 48.4% in the sacituzumab govitecan arm and 45.5% in the chemotherapy arm. Median duration of responses was 12.2 months and 7.2 months, respectively. OS data was immature at analysis. Grade ≥3 treatment-emergent adverse events occurred in 66% of patients in the sacituzumab govitecan arm and 62% of patients in the chemotherapy arm and most frequently included neutropenia (43%) and diarrhea (9%) in the sacituzumab govitecan arm and neutropenia (41%) and anemia (16%) in the chemotherapy arm. Treatment-emergent adverse events led to dose reductions in 37% of patients in the sacituzumab govitecan arm and 45% of patients in the chemotherapy arm and led to treatment discontinuation in 4% and 12% of patients, respectively.
“These data support [sacituzumab govitecan] as a potential new standard of care for [patients] with previously untreated [metastatic] TNBC who are unable to receive a [PD-L1 inhbitor].”
Source:
Cortes J, Bardia A, Punie K, et al. Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA20
