{"entity":{"id":"destiny-breast09","kind":"trial","name":"DESTINY-Breast09","aka":[],"tldr":"Showed Enhertu plus pertuzumab beats the decade-old first-line standard for HER2-positive metastatic breast cancer.","summary":"DESTINY-Breast09, trial NCT04784715 sponsored by Daiichi Sankyo and AstraZeneca and reported in 2025, showed that trastuzumab deruxtecan plus pertuzumab beats the decade-old first-line standard of a taxane, trastuzumab and pertuzumab for HER2-positive metastatic breast cancer. It randomised 1,157 patients across three arms, met its primary progression-free survival endpoint by blinded review for the combination against THP with a large effect and a higher response rate, with overall survival immature but trending favourably, while the trastuzumab deruxtecan monotherapy arm remained blinded. OnCo links it to HER2-positive breast cancer, trastuzumab deruxtecan, pertuzumab, Cristina Saura, Javier Cortés, Sara M. Tolaney and Vall d'Hebron. It replaces the CLEOPATRA-era regimen, and whether the ADC alone would do as well as the combination is the question the blinded arm will answer.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT04784715","url":"https://clinicaltrials.gov/study/NCT04784715"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["cristina-saura","javier-cortes","sara-tolaney"],"bottlenecks":[],"keyPapers":["paper-destiny-breast09-n-engl-j-med-2026"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04784715","phase":"3","setting":"First-line HER2+ metastatic breast cancer: T-DXd + pertuzumab vs THP","sponsor":"Daiichi Sankyo / AstraZeneca","result":"PFS HR 0.56.","started":"2021-04-26","startedType":"actual","yearReported":2025,"enrolled":1157,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR), T-DXd + pertuzumab vs THP","primary":true,"unit":"months","arms":[{"name":"Trastuzumab deruxtecan + pertuzumab","n":383,"value":40.7},{"name":"Taxane + trastuzumab + pertuzumab","n":387,"value":26.9}],"hr":0.56,"ci":[0.44,0.71],"p":"<0.00001","source":"https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA1008"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Trastuzumab deruxtecan + pertuzumab","value":85.1},{"name":"Taxane + trastuzumab + pertuzumab","value":78.6}],"source":"https://doi.org/10.1056/NEJMoa2508668"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Trastuzumab deruxtecan + pertuzumab","note":"Immature at the interim analysis; early trend favoured T-DXd + pertuzumab."},{"name":"Taxane + trastuzumab + pertuzumab"}],"source":"https://doi.org/10.1056/NEJMoa2508668"}],"replication":"Single pivotal trial versus the CLEOPATRA-era standard; the T-DXd monotherapy arm is still blinded. Consistent with the class's performance in DESTINY-Breast03."},"route":"/trials/destiny-breast09/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-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/"}],"drug":[{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-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":"cristina-saura","kind":"person","name":"Cristina Saura","route":"/people/cristina-saura/"},{"id":"javier-cortes","kind":"person","name":"Javier Cortés","route":"/people/javier-cortes/"},{"id":"sara-tolaney","kind":"person","name":"Sara M. Tolaney","route":"/people/sara-tolaney/"}],"paper":[{"id":"paper-destiny-breast09-n-engl-j-med-2026","kind":"paper","name":"Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer","route":"/key-papers/paper-destiny-breast09-n-engl-j-med-2026/"}],"institution":[{"id":"vall-dhebron","kind":"institution","name":"Vall d'Hebron University Hospital / VHIO","route":"/institutions/vall-dhebron/"}]}}