# Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy

Source: https://onco.cc/key-papers/paper-create-x-adjuvant-capecitabine-nejm-2017/  
OnCo record `paper-create-x-adjuvant-capecitabine-nejm-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: New England Journal of Medicine
- Year: 2017
- DOI: 10.1056/NEJMoa1612645
- Authors: Masuda N, Lee SJ, Ohtani S, et al.
- 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.
- What it means: 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.

## Sources

- N Engl J Med 2017: https://doi.org/10.1056/NEJMoa1612645
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28564564/
- UMIN Clinical Trials Registry UMIN000000843: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001028

## Connected records

- key papers: [Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy](https://onco.cc/key-papers/paper-masuda-n-engl-j-med/), [Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer](https://onco.cc/key-papers/paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008/)
- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/)
- terms: [Hazard ratio (HR)](https://onco.cc/terms/hazard-ratio/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- ideas: [ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative](https://onco.cc/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/)

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