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Breast Cancer · Medical Oncology

CREATE-X

In HER2-negative breast cancer with residual invasive disease after neoadjuvant chemotherapy, does adjuvant capecitabine improve DFS and OS?

Population
910 randomized patients with HER2-negative residual invasive breast cancer after neoadjuvant anthracycline and/or taxane chemotherapy.
Treatment
Capecitabine versus no capecitabine; protocol treatment was generally 8 cycles, with oral capecitabine given on days 1–14 of 21-day cycles.
5-year DFS
74.1% vs 67.6%; absolute benefit 6.5 points; NNT 16.
5-year OS
89.2% vs 83.6%; absolute benefit 5.6 points; NNT 18.

Absolute Effect

Primary endpoint: DFS HR 0.70 (95% CI 0.53–0.92), P=.01. OS HR 0.59 (95% CI 0.39–0.90), P=.01.

TNBC subgroup: 5-year DFS 69.8% vs 56.1% (HR 0.58, 95% CI 0.39–0.87) and OS 78.8% vs 70.3% (HR 0.52, 95% CI 0.30–0.90).

Safety/burden: Hand-foot syndrome occurred in 73.4% with capecitabine. Diarrhea and other treatment-related toxicity were increased; toxicity is best interpreted alongside the oral-treatment burden rather than converted to a generic NNH.

Interpretation & limitations

The trial was conducted in Japan and South Korea and used a postoperative strategy without contemporary immunotherapy/HER2-directed escalation. The strongest signal was in TNBC with residual disease.

Primary source

Masuda N, et al. N Engl J Med. 2017;376:2147–2159.

Read the primary publication →

Current-practice context · reviewed 14 October 2026

CREATE-X supports adjuvant capecitabine for selected patients with residual HER2-negative invasive breast cancer after neoadjuvant chemotherapy, with the clearest benefit in triple-negative disease. It does not apply to patients with a pathological complete response or automatically replace subtype-specific post-neoadjuvant options; contemporary decisions also consider germline BRCA status, HER2 status, prior immunotherapy and residual-risk strategy.

CREATE-X primary/long-term report ↗ · Current guideline guidance ↗