{"entity":{"id":"create-x","kind":"trial","name":"CREATE-X","aka":["JBCRG-04","CREATE-X/JBCRG-04","UMIN000000843"],"tldr":"CREATE-X showed that giving the tablet chemotherapy capecitabine for six months after surgery, to women whose breast cancer had not fully disappeared with pre-operative chemotherapy, cut deaths; the gain was largest in triple-negative disease, where five-year survival rose from 70 to 79 percent.","summary":"CREATE-X (UMIN000000843) randomised 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy containing an anthracycline, a taxane or both to standard post-surgical treatment with or without capecitabine 1,250 mg/m2 twice daily on days 1 to 14 of 21 for six to eight cycles. The trial stopped early when a prespecified interim analysis met the primary endpoint. Five-year disease-free survival was 74.1 versus 67.6 percent (hazard ratio 0.70, 95 percent confidence interval 0.53 to 0.92, p 0.01) and five-year overall survival 89.2 versus 83.6 percent (hazard ratio 0.59, 0.39 to 0.90, p 0.01). In the triple-negative subgroup disease-free survival was 69.8 versus 56.1 percent (hazard ratio 0.58, 0.39 to 0.87) and overall survival 78.8 versus 70.3 percent (hazard ratio 0.52, 0.30 to 0.90). Hand-foot syndrome occurred in 73.4 percent of the capecitabine group.\n\nCREATE-X predates immunotherapy: none of its patients had pembrolizumab, and whether capecitabine adds to adjuvant pembrolizumab after residual disease on the KEYNOTE-522 regimen has never been tested directly; it is the physician's-choice control in ASCENT-05/OptimICE-RD and TROPION-Breast03. The Spanish GEICAM/CIBOMA trial of extended adjuvant capecitabine in unselected early triple-negative disease was negative and SYSUCC-001 (metronomic capecitabine for a year) positive for disease-free survival, so the evidence for capecitabine is strongest in the CREATE-X population, residual disease after neoadjuvant chemotherapy. The trial has no ClinicalTrials.gov record; it is registered with the UMIN Clinical Trials Registry.","status":"positive","asOf":"2026-09-24","links":[{"label":"Masuda et al., NEJM 2017: adjuvant capecitabine for breast cancer after preoperative chemotherapy (CREATE-X)","url":"https://doi.org/10.1056/NEJMoa1612645"},{"label":"UMIN000000843","url":"https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001004"}],"tags":["registry:umin"],"related":[],"cancers":["tnbc","tnbc-early","breast-hr-positive"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["rcb","efs","hand-foot-syndrome","tnbc-residual-disease-decision"],"trials":["sysucc-001","geicam-ciboma","ea1131","ascent-05","tropion-breast03"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Registered as UMIN000000843 with the UMIN Clinical Trials Registry; no ClinicalTrials.gov entry. The 910 randomised patients were split 1 to 1; subgroup arm sizes are not given in the abstract.","Hand-foot syndrome, the most common adverse reaction, occurred in 73.4 percent of the capecitabine group."],"phase":"3","setting":"HER2-negative breast cancer with residual invasive disease after neoadjuvant anthracycline, taxane or both: standard post-surgical treatment with or without six to eight cycles of capecitabine, Japan and Korea","sponsor":"Japan Breast Cancer Research Group / Advanced Clinical Research Organization","result":"5-year DFS 74.1% vs 67.6% (HR 0.70); OS 89.2% vs 83.6% (HR 0.59). TNBC subgroup: DFS 69.8% vs 56.1% (HR 0.58), OS 78.8% vs 70.3% (HR 0.52).","yearReported":2017,"enrolled":910,"enrolledBasis":"registry","outcomes":[{"endpoint":"Disease-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Capecitabine","value":74.1},{"name":"Control","value":67.6}],"hr":0.7,"ci":[0.53,0.92],"p":"0.01","source":"https://doi.org/10.1056/NEJMoa1612645"},{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Capecitabine","value":89.2},{"name":"Control","value":83.6}],"hr":0.59,"ci":[0.39,0.9],"p":"0.01","source":"https://doi.org/10.1056/NEJMoa1612645"},{"endpoint":"Disease-free survival at 5 years, triple-negative subgroup","unit":"%","arms":[{"name":"Capecitabine","value":69.8},{"name":"Control","value":56.1}],"hr":0.58,"ci":[0.39,0.87],"source":"https://doi.org/10.1056/NEJMoa1612645"},{"endpoint":"Overall survival at 5 years, triple-negative subgroup","unit":"%","arms":[{"name":"Capecitabine","value":78.8},{"name":"Control","value":70.3}],"hr":0.52,"ci":[0.3,0.9],"source":"https://doi.org/10.1056/NEJMoa1612645"}],"replication":"SYSUCC-001 (metronomic capecitabine after adjuvant chemotherapy) also improved disease-free survival; GEICAM/CIBOMA in unselected early TNBC did not; EA1131 found platinum no better than capecitabine for residual disease."},"route":"/trials/create-x/","neighbours":{"cancer":[{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"}],"term":[{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"hand-foot-syndrome","kind":"term","name":"Hand-foot syndrome and hand-foot skin reaction","route":"/terms/hand-foot-syndrome/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"},{"id":"tnbc-residual-disease-decision","kind":"term","name":"Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point","route":"/terms/tnbc-residual-disease-decision/"}],"trial":[{"id":"ascent-05","kind":"trial","name":"ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)","route":"/trials/ascent-05/"},{"id":"bre12-158","kind":"trial","name":"BRE12-158 (Hoosier Oncology Group)","route":"/trials/bre12-158/"},{"id":"ea1131","kind":"trial","name":"ECOG-ACRIN EA1131","route":"/trials/ea1131/"},{"id":"geicam-ciboma","kind":"trial","name":"GEICAM/2003-11_CIBOMA/2004-01","route":"/trials/geicam-ciboma/"},{"id":"sysucc-001","kind":"trial","name":"SYSUCC-001","route":"/trials/sysucc-001/"},{"id":"tropion-breast03","kind":"trial","name":"TROPION-Breast03","route":"/trials/tropion-breast03/"}]}}