{"entity":{"id":"kristine","kind":"trial","name":"KRISTINE","aka":[],"tldr":"KRISTINE tested whether an antibody-drug conjugate could replace chemotherapy before surgery in HER2-positive breast cancer and found it could not: fewer tumours disappeared and more grew before the operation.","summary":"KRISTINE, trial NCT02131064 sponsored by Roche and Genentech and published in the Lancet Oncology in 2018, randomised 444 patients with stage II or III HER2-positive breast cancer to six cycles of trastuzumab emtansine plus pertuzumab or to docetaxel, carboplatin, trastuzumab and pertuzumab before surgery. Pathological complete response was 44.4 percent with the antibody-drug conjugate against 55.7 percent with chemotherapy, and although the conjugate arm had fewer severe side effects and better quality of life, 15 patients in that arm had locoregional progression before surgery against none with chemotherapy. The three-year follow-up in 2019 showed worse event-free survival with the conjugate driven by those pre-surgical progressions, while invasive disease-free survival after surgery was similar. The trial is the standard warning against replacing chemotherapy with an antibody-drug conjugate on the basis of response rates alone, a lesson revisited when DESTINY-Breast11 kept a chemotherapy phase after trastuzumab deruxtecan.","status":"negative","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT02131064","url":"https://clinicaltrials.gov/study/NCT02131064"},{"label":"Hurvitz et al., KRISTINE (Lancet Oncology 2018)","url":"https://doi.org/10.1016/S1470-2045(17)30716-7"}],"tags":["failure","lesson:selection"],"related":[],"cancers":["breast-her2-positive","her2-positive-early-breast-cancer"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["trastuzumab-emtansine","pertuzumab","docetaxel","carboplatin","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["pcr"],"trials":[],"people":["sara-hurvitz"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02131064","phase":"3","setting":"Stage II to III HER2-positive breast cancer: neoadjuvant trastuzumab emtansine plus pertuzumab vs docetaxel, carboplatin, trastuzumab and pertuzumab","sponsor":"Roche / Genentech","result":"Pathological complete response 44.4% (T-DM1 + pertuzumab) vs 55.7% (TCHP); more locoregional progression before surgery with T-DM1.","yearReported":2018,"enrolled":444,"outcomes":[{"endpoint":"Pathological complete response (breast and axilla)","primary":true,"unit":"%","arms":[{"name":"Trastuzumab emtansine + pertuzumab","n":223,"value":44.4},{"name":"Docetaxel, carboplatin, trastuzumab, pertuzumab","n":221,"value":55.7}],"p":"0.016","source":"https://doi.org/10.1016/S1470-2045(17)30716-7"}],"replication":"The 2019 event-free survival update confirmed the disadvantage; DESTINY-Breast11 later stopped its trastuzumab deruxtecan monotherapy arm for lower efficacy."},"route":"/trials/kristine/","neighbours":{"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/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"}],"term":[{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"person":[{"id":"sara-hurvitz","kind":"person","name":"Sara A. Hurvitz","route":"/people/sara-hurvitz/"}]}}