Sacituzumab Govitecan Extends Progression-Free Survival in Advanced Triple-Negative Breast Cancer
Key Clinical Takeaways
- Design/Population: In the phase 3 open-label ASCENT-03 trial, previously untreated patients with locally advanced or metastatic triple-negative breast cancer ineligible for PD-1/PD-L1 inhibitors (n = 558) were randomized to receive sacituzumab govitecan or investigator’s choice chemotherapy.
- Key Outcomes: Sacituzumab govitecan significantly improved PFS vs chemotherapy (9.7 vs 6.9 months; HR 0.62; P < .001), with similar objective response rates (48% vs 46%) and a longer median duration of response (12.2 vs 7.2 months).
- Clinical Relevance: The regimen provided a meaningful PFS advantage with comparable rates of grade ≥3 adverse events (66% vs 62%), most commonly neutropenia, diarrhea, anemia, and leukopenia.
Results from the phase 3 ASCENT-03 trial show that sacituzumab govitecan prolongs progression-free survival (PFS) compared to standard chemotherapy among previously untreated patients with locally advanced, unresectable or metastatic triple-negative breast cancer unable to undergo programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibition due to coexisting conditions.
In this open-label trial, 558 patients, including those with PD-L1–negative tumors (CPS <10) and PD-L1–positive tumors (CPS ≥10), were randomized 1:1 to receive either sacituzumab govitecan or investigator’s choice chemotherapy (paclitaxel, nanoparticle albumin-bound paclitaxel, or gemcitabine plus carboplatin). The primary end point was PFS, assessed via blinded independent central review. Key secondary end points included objective response rate (ORR), duration of response, and safety.
At analysis, 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 0.77; P <.001). The ORR was 48% in the sacituzumab govitecan arm and 46% in the chemotherapy arm. Median duration of response was 12.2 months and 7.2 months, respectively. Grade ≥3 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, diarrhea, anemia, and leukopenia. Adverse events led to treatment discontinuation in 4% of patients in the sacituzumab govitecan arm and 12% of patients in the chemotherapy arm.
“Sacituzumab govitecan led to significantly longer [PFS] than chemotherapy among patients with advanced triple-negative breast cancer who were not candidates for treatment with PD-1 or PD-L1 inhibitors,” concluded Dr Cortes et al. “The incidence of adverse events of grade 3 or higher with sacituzumab govitecan was similar to that with chemotherapy, but adverse events were common.”
Source:
Cortes J, Punie K, Barrios C, et al. Sacituzumab govitecan in untreated, advanced triple-negative breast cancer. N Engl J Med. Published online: October 18, 2025. doi:10.1056/NEJMoa2511734
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