Matthew Kurian, Assistant Professor of Medicine at the University of Kentucky College of Medicine and Physician at St. Elizabeth Healthcare, shared a post on LinkedIn:
“ESMO25 | TROP2 ADC Showdown in 1L mTNBC
Two phase III studies — ASCENT-03 (Trodelvy) and TROPION-Breast02 (Datopotamab-DXd) — highlight how trial design can shape outcomes
ASCENT-03
- mPFS 9.7 vs 6.9 mo (HR 0.62)
- Crossover allowed after BICR progression
- OS immature but trending favorable
- AEs: diarrhea + neutropenia, lower discontinuation rate
TROPION-Breast02
- mPFS PFS 10.8 vs 5.6 mo, HR 0.57 (p<0.001)
- OS 23.7 vs 18.7 mo, HR 0.79 (SS)
- Included poorer-prognosis pts (15% relapsed < 6 mo after neoadj/adj tx)
- No doublet chemo, No ADC crossover
- OS signal looked weaker in regions with TROP2 ADC access
Discussion at ESMO25:
- Crossover in ASCENT-03 may blunt OS differences but mirrors real-world access
- TB-02’s tighter design may show “cleaner” OS but harsher baseline biology
- Safety trade-offs: SG → GI / neutropenia | Dato-DXd → mucositis / ocular toxicity
- 60-70% of population outside of US/Europe
Takeaway:
Both deliver meaningful PFS benefit — but for now, Trodelvy leads the pack in PD-L1–negative / IO-ineligible mTNBC.
Dato-DXd may close the gap as OS and QoL data mature.
AEs become more important here
We need resistance markers for sequencing.”
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