Impact of  ADCs in Early TNBC Treatment

Mariam Haji Ahmad, MBBCh Roswell Park Comprehensive Cancer Center | Alexis Levee, MD UCLA Health

January 17, 2026

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Key Points

  • Antibody-drug conjugates (ADCs) improved outcomes versus chemotherapy as first-line therapy in advanced or metastatic triple-negative breast cancer (TNBC).

  • Once patients have received one ADC, additional ADCs show worse efficacy, although sandwiching chemotherapy between two ADCs may improve outcomes.

  • More data are needed to explain the mechanisms of treatment resistance and optimal sequencing of ADCs in TNBC.

First-Line ADCs for Metastatic TNBC

At the 2025 San Antonio Breast Cancer Symposium, Mariam Haji Ahmad, MBBCh, of Roswell Park Comprehensive Cancer Center, and Alexis Levee, MD, of UCLA Health, discussed the movement of ADCs into earlier treatment settings for TNBC and the effect of this shift on the overall treatment algorithm.

Recently, the ASCENT-03 and ASCENT-04/KEYNOTE-D19 trials reported on sacituzumab govitecan, and the TROPION-Breast02 trial reported on datopotamab deruxtecan as first-line therapies for locally advanced or metastatic TNBC. In all three trials, treatment with either anti-TROP-2 ADC improved outcomes compared with chemotherapy. Trials are also exploring ADCs in early-stage breast cancer, although data are not yet available.

While moving ADCs into earlier treatment settings for breast cancer appears promising, its impact on treatment sequencing is unclear, particularly as more ADCs become available. Notably, retrospective data show that, after the first ADC exposure, subsequent ADCs yield inferior progression-free survival. Research is ongoing, but data from some small studies suggest that alternating chemotherapy with ADCs may improve outcomes, Dr. Levee said.