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: The SYSUCC-001 Randomized Clinical Trial

Abstract

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed.

Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer.

Design, setting, and participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy.

Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy.

Main outcomes and measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events.

Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, 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 disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event.

Conclusions and relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival.

Trial registration: ClinicalTrials.gov Identifier: NCT01112826.

Figure 1.. Flow of Patients Through the SYSUCC-001 Trial of Capecitabine for Triple-Negative Breast Cancer

Figure 2.. Kaplan-Meier Estimates of Disease-Specific Mortality, Total Mortality, Distant Disease-Specific Mortality, and Locoregional Recurrence-Specific Mortality in 434 Patients With Triple-Negative Breast Cancer

Median observation for all curves was 61 months (interquartile range, 44-82). Cumulative survival probabilities were estimated using the Kaplan-Meier analysis method and compared using log-rank tests. Hazard ratios with 95% CIs were estimated using the Cox proportional hazards model.

Figure 3.. Subgroup Analysis of Disease-Specific Mortality in 434 Patients With Triple-Negative Breast Cancer

Using the unadjusted Cox model, exploratory subgroup analyses were conducted to estimate hazard ratios with 95% CIs and to test for interactions among subgroups using 2-sided P values. The median observation was 61 months. ^aTumor size at diagnosis was based on pathological assessment. ^bHistological grade at diagnosis was based on the degree of tumor’s histologic differentiation. ^cKi-67 index at diagnosis indicates DNA synthetic activity as measured by immunocytochemistry.