Anti-TROP-2 ADCs in PD-L1-Negative TNBC

Alexis Levee, MD UCLA Health | Paolo Tarantino, MD Dana-Farber Cancer Institute

January 1, 2026

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Key Points

  • Sacituzumab govitecan and datopotamab deruxtecan (Dato-DXd), anti-TROP-2 antibody-drug conjugates (ADCs), are being investigated for the treatment of metastatic triple-negative breast cancer (TNBC).

  • Both ADCs showed positive survival data in the first-line setting for PD-L1-negative metastatic TNBC.

  • ADC selection considers side-effect profiles, dosing schedules, and supportive care requirements.

Sacituzumab Govitecan and Dato-DXd in Metastatic TNBC

At the 2025 San Antonio Breast Cancer Symposium, Alexis LeVee, MD, of UCLA Health, interviewed Paolo Tarantino, MD, of Dana-Farber Cancer Institute, about anti-TROP-2 ADCs as first-line treatment for metastatic TNBC. The current ADCs in this space are sacituzumab govitecan and Dato-DXd. Both sacituzumab govitecan and Dato-DXd showed positive progression-free survival data for PD-L1-negative metastatic TNBC in the first-line setting. For PL1-positive disease, data are only available for sacituzumab govitecan plus pembrolizumab.

The key factor in deciding between the two is their different side-effect profiles. Prior interstitial lung disease might contraindicate Dato-DXd, while prior severe neutropenia might contraindicate sacituzumab govitecan. Most patients will not have absolute contraindications, so physicians should offer both and review the different toxicities, schedules, and required prophylaxis, said Dr. Tarantino. Sacituzumab govitecan is given twice every 3 weeks and requires prophylactic growth factor support. Dato-DXd is given once every 3 weeks and requires prophylactic mouthwash and ophthalmological monitoring. 

The doctors also discussed the ongoing search for effective biomarkers to select patients for anti-TROP-2 ADCs. TROP-2 immunohistochemistry was not a strong predictor of outcomes in clinical trials. There was a signal for BRCA mutations with sacituzumab govitecan in the NeoSTAR trial, “but that still remains kind of a hypothesis,” Dr. Tarantino said. In the meantime, clinical biomarkers such as the extent of disease and metastatic location can help inform treatment decisions.