Screening Optimal Candidates with Operable, Early-Stage Triple-Negative Breast Cancer Benefitting from Capecitabine Maintenance: A Post-Hoc Analysis of the SYSUCC-001 Study

Abstract Background Recent clinical trials and meta-analyses suggest that addition of capecitabine to standard chemotherapy could be beneficial in early-stage triple-negative breast cancer (TNBC). We aimed to develop an individualized prediction model to quantify the clinical benefit of capecitabine maintenance in TNBC. Methods Data of patients from the SYSUCC-001 trial (NCT01112826), randomized to standard treatment with or without metronomic capecitabine maintenance, were analyzed. Candidate covariates included age, menstrual status, type of surgery, postoperative chemotherapy regimen, Ki-67 percentage, histologic grade, primary tumor size, lymphovascular invasion, node status, and capecitabine medication. The primary endpoint was disease-free survival (DFS). The nonlinear effects of continuous covariates were modeled by restricted cubic spline. A survival prediction model was constructed using Cox proportional hazards regression analysis. Results The data of 434 patients (306 in the development cohort and 128 in the validation cohort) were analyzed. The estimated 5-year DFS in the development cohort and validation cohort were 77.8% (95% CI, 72.9%-82.7%) and 78.2% (95% CI, 70.9%-85.5%), respectively. Age and node status had significant nonlinear effects on DFS. The prediction model constructed using four covariates (node status, lymphovascular invasion, capecitabine maintenance, and age) demonstrated satisfactory calibration and fair discrimination ability, with C-index of 0.722 (95% CI, 0.662–0.781) and 0.764 (95% CI, 0.668–0.859) in the development cohort and validation cohort, respectively. An easy-to-use online calculator for predicting benefit of capecitabine maintenance was also designed. Conclusions The evidence-based prediction model may help identify patients most likely to benefit from metronomic capecitabine maintenance and thus help in decision making in daily clinical practice.