{"entity":{"id":"tropion-breast01","kind":"trial","name":"TROPION-Breast01","aka":[],"tldr":"The trial that got Datroway approved in hormone-positive breast cancer, though it did not extend overall survival.","summary":"TROPION-Breast01, trial NCT05104866 sponsored by AstraZeneca and Daiichi Sankyo and reported in 2023, is the trial that got datopotamab deruxtecan approved in HR-positive, HER2-negative metastatic breast cancer after endocrine therapy and one or two chemotherapies, though it did not extend overall survival. It randomised 732 patients to datopotamab deruxtecan or chemotherapy, met its primary progression-free survival endpoint with a higher response rate, but overall survival, also a primary endpoint, was no different, and the US approval in January 2025 rested on progression alone. OnCo links it to HR-positive breast cancer, datopotamab deruxtecan, Aditya Bardia, Sara M. Tolaney, the TROP2 ADC roadmap and the TROPION-Breast01 paper on why a progression win did not translate to survival. Why the two TROP2 ADCs diverged on survival is the open question.","status":"mixed","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT05104866","url":"https://clinicaltrials.gov/study/NCT05104866"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["datopotamab-deruxtecan"],"companies":["astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["aditya-bardia","sara-tolaney"],"bottlenecks":[],"keyPapers":["paper-tropion-breast01-china-cohort-esmo-open-2026"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05104866","phase":"3","setting":"HR+/HER2- metastatic breast cancer after endocrine and 1-2 chemotherapies: Dato-DXd vs chemotherapy","sponsor":"AstraZeneca / Daiichi Sankyo","result":"PFS HR 0.63; OS HR 1.01.","started":"2021-10-18","startedType":"actual","yearReported":2023,"enrolled":732,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Datopotamab deruxtecan","n":365,"value":6.9},{"name":"Chemotherapy (ICC)","n":367,"value":4.9}],"hr":0.63,"ci":[0.52,0.76],"p":"<0.0001","source":"https://ascopubs.org/doi/10.1200/JCO.24.00920"},{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Datopotamab deruxtecan","value":18.6,"note":"Not significant"},{"name":"Chemotherapy (ICC)","value":18.3}],"hr":1.01,"ci":[0.83,1.22],"source":"https://clinicaltrials.gov/study/NCT05104866"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Datopotamab deruxtecan","value":36.4},{"name":"Chemotherapy (ICC)","value":22.9}],"source":"https://doi.org/10.1200/JCO.24.00920"}],"replication":"PFS-only benefit; the OS result did not replicate the PFS signal. The HR+ population is also served by TROPiCS-02 (sacituzumab), which did show an OS benefit."},"route":"/trials/tropion-breast01/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"drug":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"}],"person":[{"id":"aditya-bardia","kind":"person","name":"Aditya Bardia","route":"/people/aditya-bardia/"},{"id":"sara-tolaney","kind":"person","name":"Sara M. Tolaney","route":"/people/sara-tolaney/"}],"paper":[{"id":"paper-tropion-breast01-china-cohort-esmo-open-2026","kind":"paper","name":"TROPION-Breast01 China cohort: datopotamab deruxtecan versus chemotherapy in previously treated HR-positive, HER2-negative breast cancer","route":"/key-papers/paper-tropion-breast01-china-cohort-esmo-open-2026/"},{"id":"paper-tropion-breast01-jco-2024","kind":"paper","name":"TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival","route":"/key-papers/paper-tropion-breast01-jco-2024/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"},{"id":"trop2-adc-roadmap","kind":"roadmap","name":"TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET","route":"/roadmaps/trop2-adc-roadmap/"}],"term":[{"id":"group-sequential-design","kind":"term","name":"Group sequential design, stopping rules and alpha spending","route":"/terms/group-sequential-design/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"surrogate-endpoint","kind":"term","name":"Surrogate endpoint","route":"/terms/surrogate-endpoint/"},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","route":"/terms/surrogate-validation/"},{"id":"trial-failure-modes","kind":"term","name":"Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover","route":"/terms/trial-failure-modes/"}]}}