Dr Kalinsky on Safety and PRO Data With Sacituzumab Govitecan/Pembrolizumab in Previously Untreated PD-L1+ TNBC

"There are nuances in terms of the differences in…toxicities that we can see between the 2 arms, but really [these data show] a very feasible as well as clinically meaningful difference in… how long patients respond to treatment. This has led to sacituzumab govitecan plus pembrolizumab becoming a standard of care in PD-L1–positive [TNBC].”

Kevin Kalinsky, MD, MS, FASCO, a professor and director in the Division of Medical Oncology of the Department of Hematology and Medical Oncology at Emory University School of Medicine, as well as director of the Glenn Family Breast Center at Winship Cancer Institute, discussed findings from an in-depth safety analysis of the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286), which evaluated the combination of sacituzumab govitecan-hziy (Trodelvy) and pembrolizumab (Keytruda) vs chemotherapy plus pembrolizumab as frontline treatment in patients with previously untreated metastatic triple-negative breast cancer (TNBC) and positive PD-L1 expression.

Data from the safety analysis, shared during the 2025 San Antonio Breast Cancer Symposium, demonstrated a favorable benefit/risk profile for the doublet. Although treatment-emergent adverse effects (TEAEs) occurred in over 99% of patients in both the antibody-drug conjugate (ADC) and chemotherapy arms, these effects were largely consistent with the known toxicities of the individual therapies, Kalinsky noted.

The most frequent TEAEs observed with the sacituzumab govitecan and pembrolizumab combination included diarrhea, nausea, and neutropenia. In comparison, patients who received physician’s choice chemotherapy plus pembrolizumab primarily experienced neutropenia, fatigue, and anemia.Kalinsky also highlighted specific nuances in toxicity onset; for instance, patients treated with the ADC regimen developed diarrhea earlier than those in the chemotherapy group. Although the onset and duration of neutropenia were similar between the 2 arms, patients in the sacituzumab govitecan arm required higher rates of growth factor support, he added. Notably, the study confirmed that the ADC did not increase common immunotherapy-related adverse effects; rates of hypothyroidism, pneumonitis, and infusion reactions remained comparable between treatment groups.

Beyond clinical safety, patient-reported outcome (PRO) data presented at the 2025 ESMO Congress indicated that the regimen allowed patients to maintain their quality of life (QOL). The median time to first meaningful deterioration or death in physical functioning was comparable between the experimental and control arms, at 3.0 months (95% CI, 2.3-4.6) vs 3.5 months (95% CI, 2.9-4.2), respectively (HR, 0.95; 95% CI, 0.73-1.22). However, a sensitivity analysis demonstrated prolonged time to first deterioration for the sacituzumab govitecan arm, at a median of 9.3 months (95% CI, 6.1-not estimable) compared with 6.9 months (95% CI, 5.6-8.3) for chemotherapy (HR, 0.82; 95% CI, 0.60-1.11).

Kalinsky concluded that the regimen is highly feasible and provides a clinically meaningful response duration, establishing the combination of sacituzumab govitecan and pembrolizumab as a new frontline standard of care for PD-L1–positive metastatic TNBC.