# CREATE-X

Source: https://onco.cc/trials/create-x/  
OnCo record `create-x` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CREATE-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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Also known as: JBCRG-04; CREATE-X/JBCRG-04; UMIN000000843
- Tags: registry:umin
- 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
- Enrolled: 910
- 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).
- Outcomes: Disease-free survival at 5 years: Capecitabine 74.1% vs Control 67.6%, HR 0.7; Overall survival at 5 years: Capecitabine 89.2% vs Control 83.6%, HR 0.59; Disease-free survival at 5 years, triple-negative subgroup: Capecitabine 69.8% vs Control 56.1%, HR 0.58; Overall survival at 5 years, triple-negative subgroup: Capecitabine 78.8% vs Control 70.3%, HR 0.52
- 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.

## 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.

## Sources

- Masuda et al., NEJM 2017: adjuvant capecitabine for breast cancer after preoperative chemotherapy (CREATE-X): https://doi.org/10.1056/NEJMoa1612645
- UMIN000000843: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001004

## Connected records

- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/)
- terms: [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Hand-foot syndrome and hand-foot skin reaction](https://onco.cc/terms/hand-foot-syndrome/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/), [Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point](https://onco.cc/terms/tnbc-residual-disease-decision/)
- trials: [ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)](https://onco.cc/trials/ascent-05/), [BRE12-158 (Hoosier Oncology Group)](https://onco.cc/trials/bre12-158/), [ECOG-ACRIN EA1131](https://onco.cc/trials/ea1131/), [GEICAM/2003-11_CIBOMA/2004-01](https://onco.cc/trials/geicam-ciboma/), [SYSUCC-001](https://onco.cc/trials/sysucc-001/), [TROPION-Breast03](https://onco.cc/trials/tropion-breast03/)

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