Metronomic capecitabine as extended adjuvant chemotherapy for early triple-negative breast cancer (SYSUCC-001): updated 10-year outcomes and post-hoc exploratory biomarker analysis from a randomised, phase 3 trial.

Here, we provide updated 10-year disease-free survival and overall survivaldata from extended follow-up, together with an exploratory analysis of FOXC1 as a potential predictive biomarker.

在这里，我们提供了来自延长随访的最新10年无病生存率和总生存率数据，以及对FOXC1作为潜在预测生物标志物的探索性分析。

Methods

This post-hoc, long-term analysis of an open-label, multicentre, phase 3 trial was conducted at 13 centres in China.

这是一项事后分析，对一项开放标签、多中心、第三阶段试验的长期分析，该试验在中国的13个中心进行。

Eligible women with stage T1b-3 N0-3c M0 triple-negative breast cancer who had completed standard adjuvant therapy were randomly assigned (1:1) to receive oral metronomic capecitabine 650 mg/m2 twice daily for 1 year or observation.

符合条件的女性患者，患有T1b-3 N0-3c M0三阴性乳腺癌，已完成标准辅助治疗，按1:1的比例随机分配接受口服低剂量卡培他滨650 mg/m2，每日两次，持续1年，或进行观察。

Here, we report 10-year follow-up data, including all of the original prespecified trial endpoints: disease-free survival (primary outcome), overall survival, distant disease-free survival, and locoregional recurrence-free survival analysed in the full analysis set.

在此，我们报告了10年的随访数据，包括所有原始预定的试验终点：无病生存期（主要结果）、总生存期、远处无病生存期和局部区域复发无病生存期，这些数据在完整分析集中进行了分析。

Exploratory biomarker analysis of FOXC1 was undertaken using immunohistochemistry on baseline tumour samples.

我们使用免疫组化技术对基线肿瘤样本进行了FOXC1的探索性生物标志物分析。

This trial is registered with ClinicalTrials.gov, NCT01112826, and is complete.

该试验已在ClinicalTrials.gov上注册，注册号为NCT01112826，并已完成。

Results

Between April 23, 2010, and Dec 31, 2016, 443 participants were enrolled and randomly assigned, of whom 434 initiated the intervention as assigned and were included in the primary analysis (221 in the capecitabine group, 213 in the observation group).

在2010年4月23日至2016年12月31日期间，共有443名参与者被纳入并随机分配，其中434人按计划开始了干预措施，并被纳入主要分析（卡培他滨组221人，观察组213人）。

As of data cutoff for this analysis (March 31, 2025), 420 (97%) participants had available follow-up data and the median duration of follow-up was 116·0 months (IQR 96·0-134·8).

截至本次分析的数据截止日期（2025年3月31日），420名（97%）参与者有可用的随访数据，中位随访时间为116.0个月（四分位数间距96.0-134.8）。

The updated 10-year disease-free survival was significantly higher in the capecitabine group than in the observation group (78·1% vs 66·6%; hazard ratio[HR] 0·61; 95% CI 0·43-0·88; p=0·0074). 10-year overall survivalwas not significantly different between the two groups (82·4% vs 73·7%; HR 0·67; 95% CI 0·45-1·01; p=0·058).

更新的10年无病生存率在卡培他滨组显著高于观察组（78.1%对比66.6%；风险比[HR] 0.61；95%置信区间0.43-0.88；p=0.0074）。而两组的10年总生存率没有显著差异（82.4%对比73.7%；HR 0.67；95%置信区间0.45-1.01；p=0.058）。

The 10-year distant disease-free survival rates were 78·1% versus 66·5% (HR 0·61; 95% CI 0·43-0·88; p=0·0075) and 10-year locoregional recurrence-free survival rates were 81·6% versus 69·9% (0·60; 0·40-0·89; p=0·011).

10年远处无病生存率分别为78.1%和66.5%（HR 0.61；95%置信区间0.43-0.88；p=0.0075），10年局部区域无复发生存率分别为81.6%和69.9%（0.60；95%置信区间0.40-0.89；p=0.011）。

The FOXC1 biomarker cohort comprised 338 (78%) patients (171 [51%] from the capecitabine group, 167 [49%] from the observation group).

FOXC1生物标志物队列包括338名（78%）患者（卡培他滨组171名[51%]，观察组167名[49%]）。

In FOXC1-high patients (n=149), capecitabine conferred superior disease-free survival (HR 0·33; 95% CI 0·16-0·68; p=0·0027) and overall survival(0·25; 0·10-0·62; p=0·0028) compared with observation, whereas the FOXC1-low subgroup (n=189) showed no benefit with capecitabine versus observation.

在FOXC1高表达的患者(n=149)中，卡培他滨相比观察组，疾病无进展生存期(HR 0·33; 95% 置信区间 0·16-0·68; p=0·0027)和总生存期(0·25; 95% 置信区间 0·10-0·62; p=0·0028)均有显著改善，而在FOXC1低表达的亚组(n=189)中，卡培他滨与观察组相比没有显示出益处。

interpretation

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.

在这项探索性的长期分析中，延长辅助治疗的卡培他滨在早期三阴性乳腺癌中提供了持久的疾病无进展生存益处，但鉴于分析的回顾性本质，这些发现应谨慎解读。

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.

FOXC1高表达肿瘤患者在接受卡培他滨治疗后显示出生存优势，与观察组相比；如果这一发现得到验证，基于FOXC1的患者选择可能有助于优化治疗反应。

funding

National Natural Science Foundation of China and Guangdong Esophageal Cancer Institute Science and Technology Program.

国家自然科学基金和广东省食管癌研究所科技计划。

translation

For the Chinese translation of the abstract see Supplementary Materials section.

摘要的中文翻译请参见补充材料部分。