# DESTINY-Breast06

Source: https://onco.cc/trials/destiny-breast06/  
OnCo record `destiny-breast06` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Moved Enhertu ahead of chemotherapy in hormone-positive breast cancer and extended it to 'ultralow' HER2.

## Summary

DESTINY-Breast06, trial NCT04494425 sponsored by Daiichi Sankyo and AstraZeneca and published in the New England Journal of Medicine in 2024, moved trastuzumab deruxtecan ahead of chemotherapy in HR-positive, HER2-low breast cancer after endocrine therapy and extended it to HER2-ultralow tumours. It randomised 866 chemotherapy-naive patients to trastuzumab deruxtecan or chemotherapy, met its primary progression-free survival endpoint in HER2-low disease with a similar benefit in the ultralow group and a much higher response rate, and was approved in 2025. It replicates DESTINY-Breast04 in an earlier line, and whether any HER2 expression threshold matters at all is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-04
- Registry id: NCT04494425
- Phase: 3
- Setting: HR+ HER2-low/ultralow breast cancer after endocrine therapy, chemotherapy-naive: T-DXd vs chemotherapy
- Sponsor: Daiichi Sankyo / AstraZeneca
- Enrolled: 866
- Result: PFS HR 0.62.
- Outcomes: Progression-free survival, HER2-low (BICR): Trastuzumab deruxtecan 13.2 months vs Chemotherapy (TPC) 8.1 months, HR 0.62; Progression-free survival, ITT (HER2-low + ultralow): Trastuzumab deruxtecan 13.2 months vs Chemotherapy (TPC) 8.1 months, HR 0.63; Objective response rate, HER2-low: Trastuzumab deruxtecan 56.5% vs Chemotherapy (TPC) 32.2%
- Replication: Replicates DESTINY-Breast04 in an earlier line and extends it to HER2-ultralow.

## Sources

- ClinicalTrials.gov NCT04494425: https://clinicaltrials.gov/study/NCT04494425

## Connected records

- cancers: [HER2-low and HER2-ultralow metastatic breast cancer](https://onco.cc/cancers/her2-low-metastatic-breast-cancer/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [HR-positive metastatic breast cancer after CDK4/6 inhibitors](https://onco.cc/cancers/hr-positive-metastatic-post-cdk46/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- drugs: [HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)](https://onco.cc/drugs/her2-testing-assays/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Daiichi Sankyo](https://onco.cc/companies/daiichi-sankyo/)
- terms: [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/)
- people: [Giuseppe Curigliano](https://onco.cc/people/giuseppe-curigliano/)
- key papers: [DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer](https://onco.cc/key-papers/paper-destiny-breast06-nejm-2024/)
- pairings: [HER2-low scoring → T-DXd](https://onco.cc/pairings/her2-low-to-tdxd/)
- ideas: [AI quantification of HER2-low and HER2-ultralow](https://onco.cc/ideas/idea-ai-her2-low-scoring/), [Calibrated reference slides so every lab scores HER2-low the same way](https://onco.cc/ideas/idea-tr2-her2-low-reference-materials/), [Randomised trials to test whether biomarker-negative patients really do not benefit](https://onco.cc/ideas/idea-tr2-biomarker-negative-arms/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/)
- roadmaps: [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/)

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