# DESTINY-Breast03

Source: https://onco.cc/trials/destiny-breast03/  
OnCo record `destiny-breast03` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The head-to-head ADC trial where Enhertu beat Kadcyla by a wide margin, showing that payload and bystander effect matter.

## Summary

DESTINY-Breast03, trial NCT03529110 sponsored by Daiichi Sankyo and AstraZeneca and reported in 2021, was the head-to-head antibody-drug conjugate trial in which trastuzumab deruxtecan beat trastuzumab emtansine by a wide margin in HER2-positive metastatic breast cancer after trastuzumab and a taxane, showing that payload and bystander effect matter. It randomised 524 patients, met its primary progression-free survival endpoint by blinded review with a very large effect and a much higher response rate, and showed an overall survival benefit, redefining second-line HER2-positive therapy and validating the DXd platform. OnCo links it to HER2-positive breast cancer, both drugs, Ian E. Krop, Javier Cortés, Sara A. Hurvitz, Sung-Bae Kim, Vall d'Hebron, the ADC roadmap and the DESTINY-Breast03 and KATHERINE papers. Whether T-DM1 retains any role after this result is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-04
- Registry id: NCT03529110
- Phase: 3
- Setting: HER2+ metastatic breast cancer after trastuzumab and taxane: T-DXd vs T-DM1
- Sponsor: Daiichi Sankyo / AstraZeneca
- Enrolled: 524
- Result: PFS HR 0.33; OS HR 0.64.
- Outcomes: Progression-free survival (BICR): Trastuzumab deruxtecan 28.8 months vs Trastuzumab emtansine 6.8 months, HR 0.33; Overall survival: Trastuzumab deruxtecan 52.6 months vs Trastuzumab emtansine 42.7 months, HR 0.73; Objective response rate: Trastuzumab deruxtecan 78.5% vs Trastuzumab emtansine 35%
- Replication: Head-to-head ADC trial; consistent with the single-arm DESTINY-Breast01 (ORR 61%) and with DESTINY-Breast02 versus treatment of physician's choice.

## Sources

- ClinicalTrials.gov NCT03529110: https://clinicaltrials.gov/study/NCT03529110

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HER2-positive breast cancer with brain metastases](https://onco.cc/cancers/her2-positive-breast-brain-metastases/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- drugs: [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/)
- people: [Ian E. Krop](https://onco.cc/people/ian-krop/), [Javier Cortés](https://onco.cc/people/javier-cortes/), [Sara A. Hurvitz](https://onco.cc/people/sara-hurvitz/), [Sung-Bae Kim](https://onco.cc/people/kim-sung-bae/)
- key papers: [DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer](https://onco.cc/key-papers/paper-destiny-breast03-nejm-2022/), [KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment](https://onco.cc/key-papers/paper-katherine-nejm-2019/), [Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial](https://onco.cc/key-papers/paper-destiny-breast03-lancet-2023-update/)
- institutions: [Vall d'Hebron University Hospital / VHIO](https://onco.cc/institutions/vall-dhebron/)
- roadmaps: [ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs](https://onco.cc/roadmaps/adc-generations/)

---
JSON: https://onco.cc/api/v1/entities/destiny-breast03.json