{"entity":{"id":"paper-create-x-adjuvant-capecitabine-nejm-2017","kind":"paper","name":"Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy","aka":[],"tldr":"The Japanese and Korean trial of 910 women whose tumours had survived pre-surgery chemotherapy, in which six months of capecitabine tablets cut deaths by 41 percent, and by 48 percent in the triple-negative group; the first treatment ever shown to help after residual disease.","summary":"CREATE-X (Masuda, Lee, Ohtani, Im and colleagues) randomised 910 patients with HER2-negative residual invasive breast cancer after anthracycline- and/or taxane-containing neoadjuvant chemotherapy to standard post-surgical treatment with or without capecitabine; the primary endpoint was disease-free survival and the trial stopped early after a pre-specified interim analysis met it. 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 overall survival 89.2 versus 83.6 percent (hazard ratio 0.59, 0.39 to 0.90, p=0.01). Among triple-negative patients 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 (0.52, 0.30 to 0.90). Hand-foot syndrome occurred in 73.4 percent of the capecitabine group. Registered as UMIN000000843.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1612645"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28564564/"},{"label":"UMIN Clinical Trials Registry UMIN000000843","url":"https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001028"}],"tags":["tnbc-evidence"],"related":["paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008","paper-masuda-n-engl-j-med"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["rcb","neoadjuvant-adjuvant","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1612645","pmid":"28564564","authors":"Masuda N, Lee SJ, Ohtani S, et al.","paperType":"rct","findings":["Five-year disease-free survival 74.1 vs 67.6 percent; hazard ratio 0.70 (95 percent CI 0.53 to 0.92), p=0.01.","Five-year overall survival 89.2 vs 83.6 percent; hazard ratio 0.59 (0.39 to 0.90), p=0.01.","Triple-negative subgroup: disease-free survival 69.8 vs 56.1 percent (hazard ratio 0.58); overall survival 78.8 vs 70.3 percent (0.52).","Hand-foot syndrome in 73.4 percent on capecitabine."],"whatItMeans":"Established that residual disease after neoadjuvant chemotherapy is a treatable state, the principle behind OlympiA and the post-neoadjuvant antibody-drug conjugate trials; capecitabine remains the option for residual triple-negative disease without a BRCA variant in ESMO, NCCN and UK practice.","caveats":["East Asian population with different capecitabine pharmacology and tolerance from Western patients; a US confirmatory trial was never completed.","Stopped early at interim analysis, which tends to overstate effects.","Pre-immunotherapy: whether capecitabine adds to adjuvant pembrolizumab is unknown."],"changedPractice":true,"participants":910},"route":"/key-papers/paper-create-x-adjuvant-capecitabine-nejm-2017/","neighbours":{"paper":[{"id":"paper-masuda-n-engl-j-med","kind":"paper","name":"Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy","route":"/key-papers/paper-masuda-n-engl-j-med/"},{"id":"paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008","kind":"paper","name":"Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer","route":"/key-papers/paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008/"}],"cancer":[{"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/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"}],"term":[{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"idea":[{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/"}]}}