# DESTINY-Breast05

Source: https://onco.cc/trials/destiny-breast05/  
OnCo record `destiny-breast05` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Enhertu cut recurrence or death by more than half compared with Kadcyla in women with cancer left after pre-surgery treatment, replacing the KATHERINE standard.

## Summary

DESTINY-Breast05, trial NCT04622319 sponsored by Daiichi Sankyo and AstraZeneca and reported at ESMO 2025, showed that trastuzumab deruxtecan cut recurrence or death by more than half compared with trastuzumab emtansine in women with high-risk HER2-positive early breast cancer left with residual disease after pre-surgery treatment, replacing the KATHERINE standard. It randomised 1,635 women and met its primary invasive disease-free survival endpoint at an interim analysis with a large effect, at the cost of more interstitial lung disease, and the FDA approved the post-neoadjuvant indication in the second quarter of 2026 alongside the neoadjuvant DESTINY-Breast11 indication. OnCo links it to trastuzumab deruxtecan and trastuzumab emtansine, to trastuzumab brengitecan as a follower. Whether the lung toxicity is acceptable in a curative setting is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT04622319
- Phase: 3
- Setting: High-risk HER2+ early breast cancer with residual invasive disease after neoadjuvant therapy: T-DXd vs T-DM1
- Sponsor: Daiichi Sankyo / AstraZeneca
- Enrolled: 1635
- Result: 3-year iDFS 92.4% vs 83.7%, HR 0.47.
- Outcomes: 3-year invasive disease-free survival: T-DXd 92.4% vs T-DM1 83.7%, HR 0.47
- Replication: Consistent with DESTINY-Breast03 (T-DXd vs T-DM1 in metastatic disease, PFS HR 0.33).

## Sources

- ClinicalTrials.gov NCT04622319: https://clinicaltrials.gov/study/NCT04622319
- NEJM: https://pubmed.ncbi.nlm.nih.gov/41370739/

## Connected records

- cancers: [Early HER2-positive breast cancer](https://onco.cc/cancers/her2-positive-early-breast-cancer/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [Inflammatory breast cancer](https://onco.cc/cancers/inflammatory-breast-cancer/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- drugs: [Trastuzumab brengitecan](https://onco.cc/drugs/trastuzumab-brengitecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Trastuzumab emtansine](https://onco.cc/drugs/trastuzumab-emtansine/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Daiichi Sankyo](https://onco.cc/companies/daiichi-sankyo/)
- key papers: [Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer](https://onco.cc/key-papers/paper-destiny-breast05-n-engl-j-med-2026/)
- ideas: [Can T-DXd alone cure early HER2-positive disease?](https://onco.cc/ideas/idea-tdxd-first-then-nothing/)

---
JSON: https://onco.cc/api/v1/entities/destiny-breast05.json