{"entity":{"id":"paper-tropion-breast02-ann-oncol-2026","kind":"paper","name":"Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial","aka":[],"tldr":"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.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2026.03.008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41937088/"},{"label":"ClinicalTrials.gov NCT05374512","url":"https://clinicaltrials.gov/study/NCT05374512"}],"tags":["tnbc-evidence"],"related":["trop2-adc-roadmap"],"cancers":["tnbc"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["trop2"],"drugs":["datopotamab-deruxtecan"],"companies":["astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":["pfs","os","adc-sequencing"],"trials":["tropion-breast02","tropion-breast05","ascent-03"],"people":["rebecca-dent","peter-schmid","javier-cortes"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2026.03.008","pmid":"41937088","authors":"Dent R, Shao Z, Schmid P, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":644},"route":"/key-papers/paper-tropion-breast02-ann-oncol-2026/","neighbours":{"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/"}],"cancer":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"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":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"ascent-03","kind":"trial","name":"ASCENT-03","route":"/trials/ascent-03/"},{"id":"tropion-breast02","kind":"trial","name":"TROPION-Breast02","route":"/trials/tropion-breast02/"},{"id":"tropion-breast05","kind":"trial","name":"TROPION-Breast05","route":"/trials/tropion-breast05/"}],"person":[{"id":"javier-cortes","kind":"person","name":"Javier Cortés","route":"/people/javier-cortes/"},{"id":"peter-schmid","kind":"person","name":"Peter Schmid","route":"/people/peter-schmid/"},{"id":"rebecca-dent","kind":"person","name":"Rebecca Dent","route":"/people/rebecca-dent/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}],"idea":[{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","route":"/ideas/idea-tnbc-adc-sequencing-trial/"},{"id":"idea-tnbc-brain-metastasis-trials","kind":"idea","name":"Trials that include, and report, brain metastases in triple-negative breast cancer","route":"/ideas/idea-tnbc-brain-metastasis-trials/"}]}}