Maintenance low-dose capecitabine versus observation in early-stage triple-negative breast cancer: a randomized controlled trial assessing safety with exploratory survival outcomes

Abstract Background Triple-negative breast cancer (TNBC) carries a worse prognosis primarily because it does not have specific targeted therapies and is biologically aggressive, leading to a great probability of early relapse, especially involving visceral sites. At present, standard chemotherapy is the only available treatment in the adjuvant setting for early-stage triple-negative breast cancer, creating a critical need for effective maintenance strategies to reduce relapse and death rates. This study was intended to assess the impact of maintenance low-dose capecitabine for females diagnosed with early triple-negative breast cancer on safety, disease-free survival, and overall survival following completion of all standard adjuvant treatment. Methods Eligible patients were randomly assigned in a 1:1 ratio to either receive maintenance low-dose capecitabine therapy or undergo observation within one month of completing standard adjuvant treatment. Patients allocated to the intervention arm received oral capecitabine at a dose of 650 mg/m 2 twice daily, administered continuously for 12 months in a metronomic schedule. Results Seventy-five patients were randomized to maintenance capecitabine ( n = 39) or observation ( n = 36), with comparable baseline characteristics. Regarding the primary endpoint, maintenance low-dose capecitabine was generally well tolerated. The most frequent adverse event was hand–foot syndrome, occurring in 28.2% of patients, with one grade 3 case (2.6%). Other toxicities, including gastrointestinal upset, neutropenia, and thrombocytopenia, were infrequent. After a median follow-up of 32 months, 24 disease-free survival (DFS) events were recorded: six in the capecitabine group (two local recurrences and four distant metastases) and 18 in the observation group (three local recurrences and 15 distant metastases). Kaplan–Meier analysis demonstrated a significantly lower event rate in the capecitabine arm ( p = 0.003). Survival analysis demonstrated a hazard ratio of 5.3 (95% CI: 1.04–26.8). The cumulative metastasis rate was 15.4% in the capecitabine group compared with 50% in the control group ( p = 0.003). Estimated 32-month overall survival (OS) rates were 94.9% and 77.8%, respectively ( p = 0.04). Conclusions One year of maintenance low-dose capecitabine after standard adjuvant treatment was well tolerated, with hand–foot syndrome identified as the most frequent adverse event. While the trial was powered for safety, exploratory analyses also showed significant improvements in disease-free and overall survival along with reduced metastasis rates, in early-stage triple-negative breast cancer, warranting confirmation in larger, dedicated efficacy trials. Trial registration: ClinicalTrials.gov, NCT07143097. Registered 19 August 2025—Retrospectively registered, https://clinicaltrials.gov/study/NCT07143097?tab=history .