# TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival

Source: https://onco.cc/key-papers/paper-tropion-breast01-jco-2024/  
OnCo record `paper-tropion-breast01-jco-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The TROP2-directed antibody-drug conjugate Dato-DXd delayed progression compared with chemotherapy, but the final analysis did not show a statistically significant survival benefit. It is FDA-approved for previously treated, advanced hormone-receptor-positive, HER2-negative breast cancer.

## Summary

Open-label phase 3 trial of 732 patients with hormone-receptor-positive, HER2-negative metastatic breast cancer after one or two lines of chemotherapy, randomised to datopotamab deruxtecan (Dato-DXd, 6 mg/kg) or investigator's choice chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine). Dual primary endpoints were PFS by blinded review and overall survival.

PFS was improved (6.9 vs 4.9 months, HR 0.63) with fewer high-grade adverse events, but the final overall survival analysis did not show a statistically significant improvement. The trial is a cautionary example that a TROP2 ADC can beat chemotherapy on PFS in an unselected population without establishing a survival advantage.

## Fields

- Kind: Key paper
- Last checked: 2026-10-06
- Journal: Journal of Clinical Oncology
- Year: 2024
- DOI: 10.1200/JCO.24.00920
- Authors: Bardia A, Jhaveri K, Im SA, et al.
- Findings: Median PFS by blinded central review 6.9 vs 4.9 months; HR 0.63 (95% CI 0.52-0.76).; Objective response rate 36.4% vs 22.9%.; Grade 3 or higher treatment-related adverse events about 21% vs 45%; stomatitis and ocular surface events were the characteristic Dato-DXd toxicities.; Final overall survival analysis (data cut-off July 2024; published separately): HR 1.01 (95% CI 0.83-1.22), not statistically significant.; TROP2 expression by immunohistochemistry did not select responders.
- What it means: For unresectable or metastatic hormone-receptor-positive, HER2-negative breast cancer after endocrine-based therapy and chemotherapy for advanced disease, Dato-DXd is an FDA-approved option. TROPION-Breast01 showed longer progression-free survival and fewer severe treatment-related adverse events than chemotherapy; the final overall survival analysis did not show a statistically significant improvement. Approval in this setting does not establish a survival advantage or apply to postoperative early-stage disease.
- Caveats: Open-label; PFS assessed by blinded review but subsequent therapy was at physician discretion.; Post-progression therapy, including other ADCs, likely diluted any survival effect.; The population was chemotherapy-pretreated and heterogeneous; a first-line or biomarker-selected trial might behave differently.; Immunohistochemistry for TROP2 was not predictive, leaving no validated way to choose patients.

## Sources

- Bardia et al., primary TROPION-Breast01 results: https://doi.org/10.1200/JCO.24.00920
- Pistilli et al., final TROPION-Breast01 overall survival analysis: https://doi.org/10.1016/j.annonc.2025.12.017
- FDA: Dato-DXd approval, January 17, 2025: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
- ClinicalTrials.gov NCT05104866: https://clinicaltrials.gov/study/NCT05104866

## Connected records

- ideas: [Payload-class switching as the rule for ADC sequencing](https://onco.cc/ideas/idea-payload-switching/), [TROP2 PET to choose and sequence TROP2 ADCs](https://onco.cc/ideas/idea-trop2-pet-selection/)
- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- 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/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [TROPION-Breast01](https://onco.cc/trials/tropion-breast01/), [TROPION-Breast02](https://onco.cc/trials/tropion-breast02/)
- people: [Aditya Bardia](https://onco.cc/people/aditya-bardia/), [Binghe Xu](https://onco.cc/people/xu-binghe/), [Carlos Barrios](https://onco.cc/people/barrios-carlos/), [Seock-Ah Im](https://onco.cc/people/im-seock-ah/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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