ASCENT-04/KEYNOTE-D19 trial

The ASCENT-04/KEYNOTE-D19 trial is a pivotal phase 3, randomized study in the first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have PD-L1 positive tumors. A total of 443 untreated patients were enrolled and randomized to receive either sacituzumab govitecan (SG), an antibody-drug conjugate, plus pembrolizumab, or chemotherapy plus pembrolizumab. The primary endpoint of progression-free survival (PFS) has previously been reported, showing a statistically significant and clinically meaningful improvement in median PFS for the SG plus pembrolizumab arm compared with the chemotherapy plus pembrolizumab arm, establishing this combination as a promising new treatment approach. During ESMO 2025, Prof Evandro de Azambuja, medical oncologist at the Institut Jules Bordet in Brussels, presented the patient-reported outcomes of this trial.

Patients completed validated HRQoL questionnaires at baseline, on day one of each treatment cycle, and at treatment discontinuation. Importantly, questionnaire completion rates exceeded 70% across both treatment arms. Baseline scores were high, indicating that enrolled patients had a good functional status prior to treatment initiation. This high baseline presented a challenge for detecting measurable improvements in quality of life.

Findings demonstrated that time to deterioration, defined as a worsening of 13.33 points on the standard PRO scale, was similar between the SG and chemotherapy arms, indicating that SG did not have a detrimental effect on overall quality of life. More sensitive analyses using a 20-point threshold even revealed a delayed deterioration in the SG plus pembrolizumab group compared to chemotherapy plus pembrolizumab. In addition, also the time to confirmed deterioration, requiring two consecutive worsened assessments, was also prolonged with SG plus pembrolizumab.

Further assessments of changes from baseline indicated better control of psychological well-being and pain in the SG arm. However, this benefit was counterbalanced by increased gastrointestinal toxicities, particularly nausea, vomiting, and diarrhea, which are known side effects of SG. 

In summary, SG plus pembrolizumab maintains quality of life and delays functional decline in PD-L1 positive mTNBC patients. Combined with prior evidence of a superior PFS compared to pembrolizumab + chemotherapy, these data support the combination of SG and pembrolizumab as a potential new standard first-line treatment in this setting.