{"entity":{"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","aka":[],"tldr":"The TROP2-directed antibody-drug conjugate Dato-DXd delayed progression by about two months compared with chemotherapy, but patients did not live longer, which stalled its approval in 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.\n\nPFS was improved (6.9 vs 4.9 months, HR 0.63) with fewer high-grade adverse events, but the final overall survival analysis showed no difference. The trial is a cautionary example that a TROP2 ADC can beat chemotherapy on PFS in an unselected population without changing survival.","asOf":"2026-09-08","links":[{"label":"PubMed search: TROPION-Breast01","url":"https://pubmed.ncbi.nlm.nih.gov/?term=TROPION-Breast01+datopotamab+deruxtecan+Bardia"},{"label":"ClinicalTrials.gov NCT05104866","url":"https://clinicaltrials.gov/study/NCT05104866"}],"tags":[],"related":["idea-trop2-pet-selection","idea-payload-switching"],"cancers":["breast-hr-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["trop2"],"drugs":["datopotamab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["pfs","os","adc-sequencing","ihc"],"trials":["tropion-breast01","tropion-breast02"],"people":["im-seock-ah","xu-binghe","barrios-carlos"],"bottlenecks":["b-biomarker-validation","b-trial-design","b-negative-results"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/JCO.24.00920","pmid":"39265124","authors":"Bardia A, Jhaveri K, Im SA, et al.","paperType":"rct","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 (2024): no significant difference (HR close to 1.0).","TROP2 expression by immunohistochemistry did not select responders."],"whatItMeans":"For hormone-receptor-positive metastatic breast cancer that has already had chemotherapy, Dato-DXd controls the disease for longer with fewer severe side effects than chemotherapy, but does not help patients live longer, so it is not a standard option here. The result is a reminder that progression-free survival is a surrogate; regulators and clinicians should wait for survival data before adopting an ADC in a setting where later therapies are effective.","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."],"changedPractice":false,"participants":732},"route":"/key-papers/paper-tropion-breast01-jco-2024/","neighbours":{"idea":[{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","route":"/ideas/idea-payload-switching/"},{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","route":"/ideas/idea-trop2-pet-selection/"}],"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"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/"}],"target":[{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"}],"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/"}],"term":[{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","route":"/terms/adc-sequencing/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"tropion-breast01","kind":"trial","name":"TROPION-Breast01","route":"/trials/tropion-breast01/"},{"id":"tropion-breast02","kind":"trial","name":"TROPION-Breast02","route":"/trials/tropion-breast02/"}],"person":[{"id":"aditya-bardia","kind":"person","name":"Aditya Bardia","route":"/people/aditya-bardia/"},{"id":"xu-binghe","kind":"person","name":"Binghe Xu","route":"/people/xu-binghe/"},{"id":"barrios-carlos","kind":"person","name":"Carlos Barrios","route":"/people/barrios-carlos/"},{"id":"im-seock-ah","kind":"person","name":"Seock-Ah Im","route":"/people/im-seock-ah/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}