Sacituzumab Govitecan/Pembro Shows Promise in First-Line PD-L1+ mTNBC

New data from the ASCENT-04 trial (NCT05382286), presented by 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, 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).

Tolaney starts the conversation by describing the aggressive nature of TNBC, which accounts for approximately 15% of all breast cancer cases. Notably, around 40% of these TNBC tumors are PD-L1 positive. The current SOC for these patients in the metastatic setting involves chemotherapy in combination with a checkpoint inhibitor, a strategy that has typically yielded progression-free survival (PFS) rates ranging from 7 to 9 months.

However, Tolaney emphasizes a critical unmet need: a significant proportion of patients initiating first-line therapy for mTNBC do not proceed to second-line treatment due to disease progression, death, or declining health. This underscores the importance of optimizing treatment strategies in the initial, frontline setting.

The ASCENT-04 trial directly addressed this need by evaluating the efficacy of combining sacituzumab govitecan with pembrolizumab compared with the SOC of chemotherapy plus pembrolizumab in patients with PD-L1 positive mTNBC. The results of this study demonstrated a statistically significant improvement in PFS for the combination arm.

“What we saw in the trial was that the median progression-free survival for sacituzumab govitecan and pembrolizumab was 11.2 months, which was significantly better than chemotherapy and pembrolizumab, which had a PFS of 7.8 months. So, an absolute difference between the 2 arms of 3.4 months with a hazard ratio of 0.65,” explains Tolaney. “This benefit was seen across all the key subgroups, and so I think it does suggest that the combination of sacituzumab govitecan and pembrolizumab could be a potential new first-line standard of care for patients who have PD-L1–positive, metastatic triple-negative breast cancer.

When asked about how these findings further establish sacituzumab govitecan's role in the broader mTNBC treatment landscape, Tolaney explained that sacituzumab govitecan is already established as a second-line SOC based on the prior ASCENT trial. That study demonstrated improved PFS and overall survival for sacituzumab govitecan compared with chemotherapy in pre-treated mTNBC.

“Now, the ASCENT-04 study is trying to move sacituzumab govitecan from that second-line space into the frontline space, specifically for patients who have PD-L1–positive metastatic triple negative disease,” adds Tolaney.