OncLive® On Air S15 Ep43: Medical Crossfire®: The Who, When, and How of TROP2-Targeting ADCs, ICIs, and PARP Inhibition in Triple-Negative Breast Cancer
Jan 30, 2026
Heather McArthur, a medical oncologist and breast cancer trialist, discusses PARP inhibitors, immune checkpoint inhibitors, and TROP2-targeting antibody–drug conjugates for metastatic triple-negative breast cancer. She outlines pivotal trials, next-generation agents, combinations of ADCs with PARP or PD-1 therapies, and practical toxicity management and sequencing considerations.
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Sacituzumab Govitecan Transforms Later-Line Care
- Sacituzumab govitecan (ASCENT) markedly improved PFS and OS versus chemotherapy in heavily pretreated metastatic TNBC.
- Benefit occurred across TROP2 expression levels, though higher expression correlated with greater benefit.
Crossover Can Mask First-Line OS Benefits
- In ASCENT‑O3 (first-line, PD-L1–negative or ineligible patients), sacituzumab govitecan improved PFS but not OS, likely due to protocol crossover to the ADC.
- Allowing second-line access to the effective agent can dilute OS differences in first-line trials.
Test ADC+ICI In PD-L1–Negative Patients
- Consider trials evaluating whether ADCs can sensitize PD-L1–negative tumors to checkpoint blockade (e.g., SASCIO combining sacituzumab with pembrolizumab).
- Enroll PD-L1–negative patients in studies that test ADC + ICI to potentially expand immunotherapy eligibility.