In a 10-year update of a Chinese phase III trial (SYSUCC-001) reported in The Lancet Oncology, Yuan et al found that the sequential addition of metronomic capecitabine to standard adjuvant therapy continued to be associated with significant benefits in patients who had undergone surgery for early triple-negative breast cancer.
Study Details
In the open-label multicenter trial, 434 patients were randomly assigned between April 2010 and December 2016 to receive metronomic capecitabine at 650 mg/m² twice daily for 1 year (n = 221) or observation (n = 213) after completing standard adjuvant therapy. The primary analysis of the trial showed that the metronomic capecitabine group had improved 5-year disease-free survival.
Key Findings
At data cutoff for the current analysis (end of March 2025), 420 (97%) patients had available follow-up data; the median duration of follow-up was 116.0 months (interquartile range = 96.0–134.8 months).
The 10-year disease-free survival was 78.1% in the capecitabine group vs 66.6% in the observation group (hazard ratio [HR] = 0.61, 95% CI = 0.43–0.88, P = .0074).
The 10-year overall survival was 82.4% vs 73.7% (HR = 0.67, 95% CI = 0.45–1.01, P = .058). At 10 years, distant disease–free survival was 78.1% vs 66.5% (HR = 0.61, 95% CI = 0.43–0.88, P = .0075), and locoregional recurrence–free survival was 81.6% vs 69.9% (HR = 0.60, 95% CI = 0.40–0.89, P = .011).
The FOXC1 biomarker cohort consisted of 338 patients (78%), including 171 (51%) in the capecitabine group and 167 (49%) in the observation group. Among 149 FOXC1-high patients, the capecitabine group had significantly improved disease-free survival (HR = 0.33, 95% CI = 0.16–0.68, P = .0027) and overall survival (HR = 0.25, 95% CI = 0.10–0.62, P = .0028) as well as distant disease–free survival and locoregional recurrence–free survival vs the observation group. In the FOXC1-low subgroup (n = 189), no significant differences between the capecitabine group and the observation group were observed for disease-free survival (HR = 1.32, 95% CI = 0.75–2.33, P = .34), overall survival (HR = 1.39, 95% CI = 0.74–2.60, P = .31), distant disease–free survival, or locoregional recurrence–free survival.
The investigators concluded: “In this exploratory, long-term analysis, extended adjuvant metronomic capecitabine provided durable disease-free survival benefit in early triple-negative breast cancer, although the findings should be interpreted with caution given the post-hoc nature of the analysis. Patients with FOXC1-high tumours showed a survival advantage with capecitabine versus observation; if this finding is validated, FOXC1-driven patient selection might be useful to optimise therapeutic responses.”
Zhong-Yu Yuan, MD, of the Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Natural Science Foundation of China and Guangdong Esophageal Cancer Institute Science and Technology Program. For full disclosures of all study authors, visit thelancet.com.
