ADCs in TNBC: Current Data and Unanswered Questions

Pietro De Placido, MD Dana-Farber Cancer Institute | Dionisia Quiroga, DO, PhD, FASCO The Ohio State University

January 15, 2026

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Key Points

  • Antibody-drug conjugates (ADCs) like sacituzumab govitecan have a growing role in the treatment of triple-negative breast cancer (TNBC).

  • Sacituzumab govitecan with pembrolizumab improved outcomes for PD-L1–positive metastatic TNBC compared with conventional chemotherapy plus pembrolizumab.

  • ADC selection should be a shared decision based on treatment logistics and a patient’s preferences.

New Data Generated for ADCs in TNBC

Pietro De Placido, MD, of Dana-Farber Cancer Institute, interviewed Dionisia Quiroga, DO, PhD, of The Ohio State University, at the 2025 San Antonio Breast Cancer Symposium on current ADC data in TNBC and where these agents fit into the overall breast cancer treatment landscape. 

In TNBC, sacituzumab govitecan has among the most robust data among the available ADCs. The phase 3 ASCENT-04/KEYNOTE-D19 trial found that sacituzumab govitecan with pembrolizumab improved outcomes compared with conventional chemotherapy with pembrolizumab for patients with PD-L1–positive metastatic TNBC. When using this regimen, oncologists should review the unique side effects and treatment logistics with patients, but the data are compelling, and Dr. Quiroga said she routinely discusses this option in her practice. Moving forward, ADCs may also offer the first effective immunotherapy regimens for PD-L1–negative TNBC, if trial data are positive, Dr. Quiroga said.

Based on the currently available data, selection among ADCs should be guided by patient preferences and individual treatment goals. Trastuzumab deruxtecan has been appealing to many eligible patients because of its once-weekly administration and its lower alopecia rate, Dr. Quiroga said. 

The correct sequencing for ADCs and other therapies in TNBC is a central unanswered question, especially given that many patients with advanced disease do not make it to a second line of treatment. While a chemotherapy “sandwich” between two ADCs is a potential strategy, data suggest that the second ADC tends to be less effective and provides a shorter duration of benefit.

Overall, biomarker studies are needed to guide personalized treatment decisions for this very heterogeneous population, the doctors said.