Dr Tolaney on Updated Safety Findings With Sacituzumab Govitecan Plus Pembrolizumab in PD-L1–Positive TNBC

“What we saw with the sacituzumab govitecan plus pembrolizumab combination was that there was really no additive toxicity. In fact, when you look at the number of immune-related AEs, numerically there were fewer immune-related AEs with sacituzumab govitecan plus pembrolizumab compared with chemotherapy plus pembrolizumab, [which] I thought was very reassuring.”

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, summarized updated safety findings from the phase 3 ASCENT-04 trial (NCT05382286) evaluating sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) in patients with PD-L1–positive triple-negative breast cancer (TNBC), building on data from the study previously reported earlier in 2025.

According to Tolaney, a central takeaway from the updated ASCENT-04 analysis presented at the 2025 San Antonio Breast Cancer Symposium was the reassuring safety profile of the sacituzumab govitecan plus pembrolizumab combination, particularly in comparison with immune-related adverse effects (AEs) reported with chemotherapy plus pembrolizumab in the control arm. Findings showed that the incidence of grade 3 or higher treatment-emergent AEs (TEAEs) was higher in the experimental arm (n = 221) at 71% (exposure-adjusted incidence rate [EAIR], 2.19; 95% CI, 1.86-2.56) vs 70% (EAIR, 2.13; 95% CI, 1.81-2.49) in the control arm (n = 220). However, TEAEs led to dose reductions of sacituzumab govitecan in 35% of patients (EAIR, 0.62; 95% CI, 0.49-0.78) vs 44% of patients who required a chemotherapy dose reduction (EAIR, 0.94; 95% CI, 0.76-1.15).

Importantly, the updated data demonstrated no evidence of additive or synergistic toxicity when sacituzumab govitecan was combined with pembrolizumab, Tolaney said.

Immune-related AEs were observed in 30% of patients treated with sacituzumab govitecan plus pembrolizumab compared with 40% of those given chemotherapy plus pembrolizumab. This finding was notable, as it suggests that replacing conventional chemotherapy with an antibody-drug conjugate backbone may mitigate some immune-mediated toxicity without disrupting antitumor activity.

These updated safety results reinforce earlier observations presented at the 2025 ASCO Annual Meeting, where the combination demonstrated manageable toxicity and encouraging efficacy in the first-line PD-L1–positive TNBC population.