OnCo
ideasIdea

Can T-DXd alone cure early HER2-positive disease?

If Enhertu produces complete responses in two-thirds of patients before surgery, a trial should test whether some need no chemotherapy, antibodies, or even radiation afterwards.

DESTINY-Breast11 (neoadjuvant T-DXd → THP, pCR 67%) and DESTINY-Breast05 (post-neoadjuvant) bracket the curative setting. A response-adapted trial could give T-DXd alone, assess pCR (with PET or ctDNA), and de-escalate everything else for responders.

Hypothesis
Neoadjuvant T-DXd monotherapy followed by response-adapted de-escalation (no further chemotherapy; antibodies only, or observation) achieves 3-year iDFS ≥92% in pCR patients.
Rationale
pCR after HER2-directed therapy predicts near-cure; PHERGain proved imaging-adapted omission is feasible; T-DXd's pCR rate approaches the best chemotherapy-containing regimens.
What would test it
Single-arm then randomised de-escalation study with ctDNA and PET as early response markers; ILD monitoring as the safety endpoint.
Maturity
early clinical

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cancers

1
HER2-positive breast cancer

drugs

3
ApprovedMonoclonal antibody (anti-HER2, dimerisation domain)
Pertuzumab · Perjeta; Phesgo (with trastuzumab, subcutaneous)
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu

terms

1
Pathologic complete response (pCR)

trials

3
DESTINY-Breast05DESTINY-Breast11PHERGain