Dr Tolaney on ASCENT-04 Data in First-Line PD-L1+ mTNBC

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and the associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute; as well as an assistant professor of medicine at Harvard Medical School, discusses new data from the ASCENT-04 trial (NCT05382286) and their implications for community oncologists.

Shared by Tolaney in a press briefing ahead of the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, the ASCENT-04 study is showing the potential of combining sacituzumab govitecan-hziy (Trodelvy) with pembrolizumab (Keytruda) as a new first-line standard of care (SOC) for patients with PD-L1–positive metastatic triple-negative breast cancer (mTNBC). The ASCENT-04 trial evaluated the efficacy of this combination and revealed a significant improvement in progression-free survival (PFS), suggesting that it could become a strong contender for the new SOC in the frontline setting for patients with PD-L1–positive mTNBC.

Findings showed that at a data cutoff date of March 3, 2025, the sacituzumab govitecan plus pembrolizumab combination (n = 221) led to a median PFS of 11.2 months (95% CI, 9.3-16.7) by blinded independent central review (BICR) vs 7.8 months (95% CI, 7.3-9.3) with chemotherapy plus pembrolizumab (n = 222), translating to a 35% reduction in the risk of disease progression or death (HR, 0.65; 95% CI, 0.51-0.84; P <.001). The 6- and 12-month PFS rates in the sacituzumab govitecan arm were 72% (95% CI, 65%-77%) and 48% (95% CI, 41%-56%), respectively; in the chemotherapy arm, these respective rates were 63% (95% CI, 56%-69%) and 33% (95% CI, 26%-40%).

Tolaney emphasized the importance for community oncologists to identify patients with PD-L1–positive disease at the time of diagnosis.

“When patients are diagnosed with metastatic triple-negative breast cancer, it is really important to understand which patients have PD-L1–positive disease, since this would help us figure out which patients could benefit from checkpoint inhibition,” she explains.

If regulatory approval follows, the combination of sacituzumab govitecan and pembrolizumab may be considered a preferred first-line treatment for this patient population. “To me, it seems like it would be a very good first-line standard of care choice, because it is associated with a significant improvement in progression-free survival for our patients,” she adds.

These findings could mark a pivotal shift in treatment paradigms and underscore the need for timely PD-L1 testing in clinical practice.