Low-Dose Capecitabine Maintenance Therapy Leads to Improved Disease-Free Survival for TNBC

Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year resulted in significantly improved disease-free survival rates compared with observation.

Results from the randomized phase 3 SYSUCC-001 trial (NCT01112826) published in JAMA indicated that among women with early-stage triple-negative breast cancer (TNBC) who received standard adjuvant treatment, low-dose capecitabine (Xeloda) maintenance therapy for 1 year resulted in a significantly improved 5-year disease-free survival (DFS) rate compared with observation.1

Importantly, the observed treatment effects on DFS were consistent across all patient subgroups. However, the agent did not result in a significant improvement in overall survival (OS) or locoregional recurrence-free survival.

“The current trial demonstrated that a year of capecitabine was tolerable for most women without significant treatment discontinuation due to toxicity,” wrote the study authors led by Xi Wang, MD. “More than 80% of participants completed a year of treatment and less than a quarter required any treatment interruption.”

With a final follow-up date of April 30, 2020, this clinical trial was conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016. Participants were randomized 1:1 to receive either capecitabine at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation after completion of standard adjuvant chemotherapy.

In total, 443 patients with early-stage TNBC who had completed standard adjuvant chemotherapy were included in the study, including 222 who were randomized to capecitabine and 221 to observation.

The primary end point for the study was DFS. Key secondary end points included distant DFS, OS, locoregional recurrence-free survival, and adverse events (AEs).

Of the 443 patients who were randomized, 434 (98.0%) completed the trial. With a median follow-up of 61 months (interquartile range, 44-82), a total of 94 events were reported including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group.

The estimated 5-year DFS rate was 82.8% in the capecitabine group and 73.0% in the observation group (HR, 0.64; 95% CI, 0.42-0.95; P = .03). Moreover, the estimated 5-year distant DFS rate was 85.8% versus 75.8% (HR, 0.60; 95% CI, 0.38-0.92; P = .02), the estimated 5-year OS rate was 85.5% versus 81.3% (HR, 0.75; 95% CI, 0.47-1.19; P = .22), and the estimated 5-year locoregional recurrence-free survival rate was 85.0% versus 80.8% (HR, 0.72; 95% CI, 0.46-1.13; P = .15) in the capecitabine group versus the observation group, respectively.

Regarding safety, the most common capecitabine-related AE was hand-foot syndrome occurring in 100 patients (45.2%), 17 (7.7%) of whom had a grade 3 event. Other commonly reported AEs in the capecitabine group were leucopenia (23.5%), elevated bilirubin (12.7%), abdominal pain/diarrhea (6.8%), and elevated alanine aminotransferase/aspartate transaminase levels (5.0%), all of which were grade 1/2 in severity.

In an editorial written by Heather A. Parsons, MD, MPH, a medical oncologist at Dana-Farber Cancer Institute (DFCI) and instructor of Medicine at Harvard Medical School, and Harold J. Burstein, MD, PhD, clinician and clinical investigator in the Breast Oncology Center at DFCI and Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, it was suggested that the duration of tumor response can be used to guide recommendations for capecitabine, offering treatment to women with residual cancer and giving those with complete pathological response a reprieve from additional therapy.2 The editorial authors indicated that this strategy, informed by trials such as SYSUCC-001, appears to offer more therapy to those most likely to benefit.

“Results from ongoing studies that are using molecular diagnostics to detect markers of residual risk are eagerly awaited, with the hope that they will allow more personalized treatment decisions informed by test results on every patient,” the editorial authors concluded.


1. Wang X, Wang S, Huang H, et al. Effect of capecitabine maintenance therapy using lower dosage and higher frequency vs observation on disease-free survival among patients with early-stage triple-negative breast cancer who had received standard treatment. Published online December 10, 2020. JAMA. doi: 10.1001/jama.2020.23370

2. Parsons HA, Burstein HJ. Adjuvant capecitabine in triple-negative breast cancer. Published online December 10, 2020. JAMA. doi: 10.1001/jama.2020.23371.