Breast cancer · Advanced / metastatic · Phase III · N=443

ASCENT-04 / KEYNOTE-D19

In previously untreated, PD-L1-positive, unresectable locally advanced or metastatic triple-negative breast cancer, sacituzumab govitecan plus pembrolizumab was compared with chemotherapy plus pembrolizumab.

11.2 vs 7.8 moMedian progression-free survival (BICR)
HR 0.6595% CI 0.51–0.84; P<0.001
60% vs 53%Objective response rate
ImmatureOverall survival; no OS benefit estimate presented

Design, population and treatment

Design: Phase III randomised trial; 443 participants.

Population: First-line PD-L1-positive unresectable locally advanced or metastatic triple-negative breast cancer.

Experimental arm: Sacituzumab govitecan plus pembrolizumab.

Comparator: Chemotherapy plus pembrolizumab.

Primary endpoint: Progression-free survival assessed by blinded independent central review (BICR).

Registry: NCT05382286.

Key efficacy outcome

Median progression-free survival

Reported medians in months. These bars compare median durations; they are not Kaplan–Meier event-free probabilities.

Sacituzumab govitecan + pembrolizumab11.2 months
Chemotherapy + pembrolizumab7.8 months
+3.4 monthsDifference between reported median PFS values
35% lowerRelative hazard of progression or death (1 − HR); not an absolute risk reduction

Hazard ratio for progression or death

HR 0.65 (95% CI 0.51–0.84). Values below 1 favour sacituzumab govitecan plus pembrolizumab.

0.250.51.0 · no difference1.5

The confidence interval excludes 1.0, consistent with a statistically significant PFS benefit.

Safety and absolute effect

Grade ≥3 adverse events were reported in approximately 71% versus 70%; adverse-event-related discontinuation was 12% versus 31% (experimental versus comparator arm, respectively).

Absolute-effect interpretation: A valid NNT cannot be calculated from median PFS values or the hazard ratio alone. Fixed-time PFS rates are not supplied in the data used for this page. No NNT/NNH pictogram is therefore shown.

Interpretation and limitations

The trial reported a statistically significant improvement in BICR-assessed median PFS with sacituzumab govitecan plus pembrolizumab. The absolute difference between medians was 3.4 months.

Overall survival was immature at the reported analysis. ORR was 60% versus 53%. Median PFS should not be interpreted as a fixed-time absolute benefit, and the HR should not be converted into an NNT.

Current practice context — reviewed 14 November 2026

Primary-publication details and the reported efficacy and safety results were checked in this repair pass. The current guideline position and sequencing relative to contemporary first-line triple-negative breast cancer standards were not independently re-reviewed here; this page summarises trial evidence and should not be read as a guideline recommendation.

Primary source

Primary publication · DOI: 10.1056/NEJMoa2508959

Trial registry: NCT05382286.