Matthew Kurian
Matthew Kurian/youtube.com

Matthew Kurian: ESMO25 – TROP2 ADC Showdown in 1L mTNBC 

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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