{"entity":{"id":"paper-katherine-nejm-2019","kind":"paper","name":"KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment","aka":[],"tldr":"Women whose HER2-positive breast cancer was still present at surgery after chemotherapy and trastuzumab had half the risk of relapse if their post-surgery treatment was switched to the antibody-drug conjugate T-DM1 instead of continuing trastuzumab.","summary":"Open-label phase 3 trial of 1,486 patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axilla after neoadjuvant taxane- and trastuzumab-based therapy, randomised to 14 cycles of adjuvant trastuzumab emtansine (T-DM1) or trastuzumab. Primary endpoint was invasive disease-free survival.\n\nThree-year iDFS was 88.3% vs 77.0% (HR 0.50). Later follow-up confirmed an overall survival benefit. It established the response-adapted strategy: treat before surgery, then escalate only for those with residual disease.","asOf":"2026-09-08","links":[{"label":"NEJM 2019","url":"https://doi.org/10.1056/NEJMoa1814017"},{"label":"ClinicalTrials.gov NCT01772472","url":"https://clinicaltrials.gov/study/NCT01772472"}],"tags":[],"related":["idea-post-neoadjuvant-adc"],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc"],"targets":["her2"],"drugs":["trastuzumab-emtansine","trastuzumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["pcr","rcb","neoadjuvant-adjuvant"],"trials":["destiny-breast03","destiny-breast11"],"people":["gunter-von-minckwitz","sibylle-loibl","shao-zhi-ming","charles-geyer"],"bottlenecks":["b-dormancy-mrd","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1814017","authors":"von Minckwitz G, Huang CS, Mano MS, et al.","paperType":"rct","findings":["Three-year invasive disease-free survival 88.3% with T-DM1 vs 77.0% with trastuzumab, an 11.3-point gain; HR 0.50 (95% CI 0.39-0.64).","Distant recurrence as first event 10.5% vs 15.9%.","Benefit was consistent across hormone-receptor status, extent of residual disease, and prior pertuzumab use.","Long-term follow-up confirmed a significant overall survival benefit (HR about 0.66).","More grade 3 or higher adverse events with T-DM1 (25.7% vs 15.4%), notably thrombocytopenia and neuropathy."],"whatItMeans":"HER2-positive breast cancer is now routinely treated before surgery so that the pathology result can guide what comes after: patients with no residual cancer continue trastuzumab (with or without pertuzumab), while those with residual disease switch to T-DM1. This model of using the tumour's response as a test has since been copied in triple-negative and other cancers.","caveats":["Open-label design.","A minority of patients had received pertuzumab before surgery, fewer than in current practice.","Whether adding tucatinib or switching to trastuzumab deruxtecan can further improve outcomes for residual disease is being tested (CompassHER2 RD, DESTINY-Breast05).","Brain metastases as a first site of relapse were not reduced."],"changedPractice":true,"participants":1486},"route":"/key-papers/paper-katherine-nejm-2019/","neighbours":{"idea":[{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","route":"/ideas/idea-post-neoadjuvant-adc/"},{"id":"idea-her2-adc-sequencing-payload","kind":"idea","name":"Sequencing HER2 ADCs by payload after T-DXd","route":"/ideas/idea-her2-adc-sequencing-payload/"}],"cancer":[{"id":"her2-positive-early-breast-cancer","kind":"cancer","name":"Early HER2-positive breast cancer","route":"/cancers/her2-positive-early-breast-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/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"}],"trial":[{"id":"destiny-breast03","kind":"trial","name":"DESTINY-Breast03","route":"/trials/destiny-breast03/"},{"id":"destiny-breast11","kind":"trial","name":"DESTINY-Breast11","route":"/trials/destiny-breast11/"},{"id":"katherine","kind":"trial","name":"KATHERINE","route":"/trials/katherine/"}],"person":[{"id":"charles-geyer","kind":"person","name":"Charles E. Geyer Jr.","route":"/people/charles-geyer/"},{"id":"eleftherios-mamounas","kind":"person","name":"Eleftherios P. Mamounas","route":"/people/eleftherios-mamounas/"},{"id":"gunter-von-minckwitz","kind":"person","name":"Gunter von Minckwitz","route":"/people/gunter-von-minckwitz/"},{"id":"sibylle-loibl","kind":"person","name":"Sibylle Loibl","route":"/people/sibylle-loibl/"},{"id":"shao-zhi-ming","kind":"person","name":"Zhi-Ming Shao","route":"/people/shao-zhi-ming/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}