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

Abstract

for the South China Breast Cancer Group (SCBCG) 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/m 2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. MAIN OUTCOMES AND MEASURESThe 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 capecitabinerelated 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.

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021

“…As shown in a meta-analysis, only patients with TNBC and non-pCR after optimal NAST might have a benefit from the addition of capecitabine (LoE 1aa/A/AGO+). Thus, general use in TNBC cannot be recommended (LoE 1aa/A/AGO–) [56]. In TNBC, the question of adding carboplatin as a fourth substance has still not been finally clarified with regard to an OS advantage [57].…”

MCPIP1-mediated NFIC alternative splicing inhibits proliferation of triple-negative breast cancer via cyclin D1-Rb-E2F1 axis

“…TNBC patients often have poor clinical outcomes due to the high risk of early relapse and visceral metastases within 5 years 6 . The 5-year overall survival (OS) rate is about 80% in Chinese women 7 , 8 . Owing to the absence of effective targets, systematic chemotherapy remains the mainstay of TNBC patients 9 .…”

Bevacizumab Plays a double-edged role in Neoadjuvant Therapy for Non-metastatic Breast Cancer: A Systemic Review and Meta-Analysis

“…revealed that 1 year of low-dose capecitabine maintenance therapy helped to improve TNBC patients' DFS. 62 To sum up, continuous low-dose of both Bev and toxic drugs could be an optimal method to manage toxic and side effects.…”