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

Source: https://onco.cc/ideas/idea-tdxd-first-then-nothing/  
OnCo record `idea-tdxd-first-then-nothing` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

The idea is a response-adapted trial in early HER2-positive breast cancer that gives trastuzumab deruxtecan alone before surgery and, for patients who reach a pathological complete response, drops everything else: no further chemotherapy, antibodies alone or observation only. A pathological complete response predicts near-cure, PHERGain proved imaging-adapted omission is feasible, and T-DXd's complete-response rate approaches that of the best chemotherapy regimens. DESTINY-Breast11, where neoadjuvant T-DXd was followed by THP, and DESTINY-Breast05 bracket the curative setting. The test would be a single-arm study then randomised de-escalation, with PET and ctDNA as early response markers and lung toxicity as the safety endpoint.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- 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.
- Proposed test: Single-arm then randomised de-escalation study with ctDNA and PET as early response markers; ILD monitoring as the safety endpoint.
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT05113251: DESTINY-Breast11: https://clinicaltrials.gov/study/NCT05113251
- ClinicalTrials.gov NCT04622319: DESTINY-Breast05: https://clinicaltrials.gov/study/NCT04622319

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- drugs: [Pertuzumab](https://onco.cc/drugs/pertuzumab/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- trials: [DESTINY-Breast05](https://onco.cc/trials/destiny-breast05/), [DESTINY-Breast11](https://onco.cc/trials/destiny-breast11/), [PHERGain](https://onco.cc/trials/phergain/)
- key papers: [Adjuvant trastuzumab in HER2-positive breast cancer](https://onco.cc/key-papers/paper-trastuzumab-breast-her2-positive-n-engl-j-med-2011/), [Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer](https://onco.cc/key-papers/paper-hera-b31-n9831-n-engl-j-med-2005/), [Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer](https://onco.cc/key-papers/paper-trastuzumab-breast-her2-positive-n-engl-j-med-2005/)

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