{"entity":{"id":"destiny-breast03","kind":"trial","name":"DESTINY-Breast03","aka":[],"tldr":"The head-to-head ADC trial where Enhertu beat Kadcyla by a wide margin, showing that payload and bystander effect matter.","summary":"DESTINY-Breast03, trial NCT03529110 sponsored by Daiichi Sankyo and AstraZeneca and reported in 2021, was the head-to-head antibody-drug conjugate trial in which trastuzumab deruxtecan beat trastuzumab emtansine by a wide margin in HER2-positive metastatic breast cancer after trastuzumab and a taxane, showing that payload and bystander effect matter. It randomised 524 patients, met its primary progression-free survival endpoint by blinded review with a very large effect and a much higher response rate, and showed an overall survival benefit, redefining second-line HER2-positive therapy and validating the DXd platform. OnCo links it to HER2-positive breast cancer, both drugs, Ian E. Krop, Javier Cortés, Sara A. Hurvitz, Sung-Bae Kim, Vall d'Hebron, the ADC roadmap and the DESTINY-Breast03 and KATHERINE papers. Whether T-DM1 retains any role after this result is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03529110","url":"https://clinicaltrials.gov/study/NCT03529110"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["trastuzumab-deruxtecan","trastuzumab-emtansine"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["ian-krop","javier-cortes","sara-hurvitz","kim-sung-bae"],"bottlenecks":[],"keyPapers":["paper-destiny-breast03-nejm-2022","paper-destiny-breast03-lancet-2023-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03529110","phase":"3","setting":"HER2+ metastatic breast cancer after trastuzumab and taxane: T-DXd vs T-DM1","sponsor":"Daiichi Sankyo / AstraZeneca","result":"PFS HR 0.33; OS HR 0.64.","started":"2018-08-09","startedType":"actual","yearReported":2021,"enrolled":524,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Trastuzumab deruxtecan","n":261,"value":28.8},{"name":"Trastuzumab emtansine","n":263,"value":6.8}],"hr":0.33,"ci":[0.26,0.43],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02420-5/fulltext"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Trastuzumab deruxtecan","value":52.6},{"name":"Trastuzumab emtansine","value":42.7}],"hr":0.73,"ci":[0.56,0.94],"source":"https://clinicaltrials.gov/study/NCT03529110"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Trastuzumab deruxtecan","value":78.5},{"name":"Trastuzumab emtansine","value":35}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2115022"}],"replication":"Head-to-head ADC trial; consistent with the single-arm DESTINY-Breast01 (ORR 61%) and with DESTINY-Breast02 versus treatment of physician's choice."},"route":"/trials/destiny-breast03/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"}],"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":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"}],"person":[{"id":"ian-krop","kind":"person","name":"Ian E. Krop","route":"/people/ian-krop/"},{"id":"javier-cortes","kind":"person","name":"Javier Cortés","route":"/people/javier-cortes/"},{"id":"sara-hurvitz","kind":"person","name":"Sara A. Hurvitz","route":"/people/sara-hurvitz/"},{"id":"kim-sung-bae","kind":"person","name":"Sung-Bae Kim","route":"/people/kim-sung-bae/"}],"paper":[{"id":"paper-destiny-breast03-nejm-2022","kind":"paper","name":"DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer","route":"/key-papers/paper-destiny-breast03-nejm-2022/"},{"id":"paper-katherine-nejm-2019","kind":"paper","name":"KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment","route":"/key-papers/paper-katherine-nejm-2019/"},{"id":"paper-destiny-breast03-lancet-2023-update","kind":"paper","name":"Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial","route":"/key-papers/paper-destiny-breast03-lancet-2023-update/"}],"institution":[{"id":"vall-dhebron","kind":"institution","name":"Vall d'Hebron University Hospital / VHIO","route":"/institutions/vall-dhebron/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"}]}}