In the phase 3 ASCENT-04/KEYNOTE-D19 trial, sacituzumab govitecan, a TROP2-targeting antibody–drug conjugate, combined with pembrolizumab (pembro) has demonstrated significantly improved progression-free survival (PFS) over chemotherapy plus pembro in programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative breast cancer (TNBC) as a first-line treatment. This study further evaluated patient-reported outcomes (PROs) to assess the impact of sacituzumab govitecan plus pembro versus chemotherapy plus pembro on quality of life and symptom burden. The trial enrolled 443 patients with previously untreated PD-L1–positive metastatic TNBC (combined positive score ≥10), randomized 1:1 to receive sacituzumab govitecan plus pembro (n=221) or chemotherapy (gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel) plus pembro (n=222). PROs were assessed using the EORTC QLQ-C30 questionnaire, with endpoints including time to first meaningful deterioration or death (TTD) and least-squares mean (LSM) change from baseline across functional and symptom domains. A sensitivity analysis was conducted for physical functioning using a stricter threshold for meaningful change.

The analysis included 443 patients. The PRO results showed that TTD was comparable across most domains, including physical functioning (hazard ratio, 0.95; 95% confidence interval [CI], 0.73-1.22), while sacituzumab govitecan plus pembro demonstrated longer TTD for emotional functioning (hazard ratio, 0.71; 95% CI, 0.53-0.96) and pain (hazard ratio, 0.75; 95% CI, 0.57-0.98). The sensitivity analysis suggested sacituzumab govitecan plus pembro may extend TTD in physical functioning (hazard ratio, 0.82; 95% CI, 0.60-1.11). Sacituzumab govitecan plus pembro also showed greater improvements in LSM change from baseline for physical functioning (2.45; 95% CI, 0.09-4.81), role functioning (3.34; 95% CI, 0.13-6.55), emotional functioning (4.07; 95% CI, 1.20-6.93), and reduced pain (–5.39; 95% CI, –8.55 to –2.23) and insomnia (–4.59; 95% CI, –7.70 to –1.48). Worsening of nausea/vomiting (2.67; 95% CI, 0.73-4.62) and diarrhea (10.41; 95% CI, 7.53-13.29) were observed with sacituzumab govitecan plus pembro, consistent with its known safety profile. These findings highlight that sacituzumab govitecan plus pembro not only maintains overall quality of life but also improves multiple functional domains and reduces symptom burden compared with chemotherapy plus pembro. Combined with its previously demonstrated PFS benefit, sacituzumab govitecan plus pembro represents a promising new standard of care for patients with previously untreated PD-L1–positive metastatic TNBC.

Source: De Azambuja E, Schmid P, Kalinsky KM, et al. Patient-reported outcomes (PROs) with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in patients (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC) in the phase III ASCENT-04/KEYNOTE-D19 study. Presented at: ESMO Congress 2025. October 20, 2025; Berlin, Germany. Abstract LBA22.