# Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial

Source: https://onco.cc/key-papers/paper-tropion-breast02-ann-oncol-2026/  
OnCo record `paper-tropion-breast02-ann-oncol-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The trial of 644 women with newly metastatic triple-negative breast cancer who could not have immunotherapy, in which the antibody-drug conjugate datopotamab deruxtecan held the cancer still for 10.8 months against 5.6 with chemotherapy and lengthened life from 18.7 to 23.7 months.

## Summary

TROPION-Breast02 (Dent, Shao, Schmid, Cortes and colleagues) randomised 644 patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer for whom immunotherapy was not an option, between 16 May 2022 and 11 June 2024, to datopotamab deruxtecan 6 mg/kg every three weeks (323) or investigator's choice of chemotherapy (321), stratified by geography, disease-free interval and PD-L1 status; dual primary endpoints were progression-free survival by blinded independent central review and overall survival. Median progression-free survival was 10.8 months (95 percent confidence interval 8.6 to 13.0) versus 5.6 months (5.0 to 7.0), hazard ratio 0.57 (99 percent CI 0.44 to 0.73, p<0.0001); median overall survival 23.7 months (19.8 to 25.6) versus 18.7 months (16.0 to 21.8), hazard ratio 0.79 (95.01 percent CI 0.64 to 0.98, p=0.029). Grade 3 or higher treatment-related adverse events occurred in 33 versus 29 percent, led to discontinuation in 4 versus 7 percent, and there were no treatment-related deaths.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: Annals of Oncology
- Year: 2026
- DOI: 10.1016/j.annonc.2026.03.008
- Authors: Dent R, Shao Z, Schmid P, et al.
- Findings: Median progression-free survival 10.8 vs 5.6 months; hazard ratio 0.57 (99 percent CI 0.44 to 0.73), p<0.0001.; Median overall survival 23.7 vs 18.7 months; hazard ratio 0.79 (95.01 percent CI 0.64 to 0.98), p=0.029.; Grade 3 or higher treatment-related adverse events 33 vs 29 percent; discontinuation 4 vs 7 percent; no treatment-related deaths.
- What it means: The first-line overall survival result that made an antibody-drug conjugate the standard for PD-L1-negative or immunotherapy-ineligible metastatic triple-negative disease, and the reason the sequencing question (which TROP2 drug first, what after it) is now urgent.
- Caveats: Open-label design; progression-free survival was centrally reviewed to compensate.; Excluded patients eligible for immunotherapy, so it does not compare with pembrolizumab-based first-line treatment; TROPION-Breast05 does.; Interstitial lung disease is a class risk and its rate is read from the full paper, not the abstract.

## Sources

- Ann Oncol 2026: https://doi.org/10.1016/j.annonc.2026.03.008
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41937088/
- ClinicalTrials.gov NCT05374512: https://clinicaltrials.gov/study/NCT05374512

## Connected records

- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/), [TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET](https://onco.cc/roadmaps/trop2-adc-roadmap/)
- cancers: [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/)
- targets: [TROP2](https://onco.cc/targets/trop2/)
- drugs: [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Daiichi Sankyo](https://onco.cc/companies/daiichi-sankyo/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/), [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [ASCENT-03](https://onco.cc/trials/ascent-03/), [TROPION-Breast02](https://onco.cc/trials/tropion-breast02/), [TROPION-Breast05](https://onco.cc/trials/tropion-breast05/)
- people: [Javier Cortés](https://onco.cc/people/javier-cortes/), [Peter Schmid](https://onco.cc/people/peter-schmid/), [Rebecca Dent](https://onco.cc/people/rebecca-dent/)
- journals: [Annals of Oncology](https://onco.cc/journals/annals-of-oncology/)
- ideas: [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [Trials that include, and report, brain metastases in triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-brain-metastasis-trials/)

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