Low-dose capecitabine maintenance improves DFS in early-stage TNBC

The addition of low-dose capecitabine maintenance after completion of standard adjuvant chemotherapy led to significantly improved disease-free survival (DFS) among women with early-stage triple-negative breast cancer (TNBC), according to the SYSUCC-001* trial.

The researchers conducted a trial involving 434 Chinese women with early-stage TNBC (median age 46 years) at 13 academic centres and clinical sites in China between April 2010 and December 2016. Participants were randomly assigned in a 1:1 ratio to receive either oral capecitabine 650 mg/m² twice a day continuously for 1 year (n=221) or undergo observation (n=213) after completing standard adjuvant chemotherapy. [JAMA 2020;doi:10.1001/jama.2020.23370]

At a median follow-up of 61 months, overall recurrences and deaths occurred in 94 patients in the capecitabine group compared with 56 patients in the observation group.

The estimated 5-year DFS rate was significantly higher in the capecitabine group than the observation group (82.8 percent vs 73.0 percent; hazard ratio [HR] for risk of recurrence or death, 0.64; p=0.03 and 85.8 percent vs 75.8 percent; HR for distant metastasis or death, 0.60; p=0.02).

Although not significant, the capecitabine group also achieved a numerically higher rate of estimated 5-year overall survival (OS, 85.5 percent vs 81.3 percent; HR, 0.75; p=0.22) and locoregional recurrence-free survival (85.0 percent vs 80.0 percent; HR, 0.72; p=0.15) compared with the observation group.

The results were in contrast to previous randomized trials**, which failed to demonstrate improvement in either DFS or OS, as the benefit with maintenance capecitabine may be limited to TNBC patients and these trials included patients with breast cancer subtypes other than TNBC, noted the researchers. [J Clin Oncol 2012;30:11-18; Clin Cancer Res 2015;21:4305-4311; J Clin Oncol 2020;38:203-213]

Hand-foot syndrome was the most common capecitabine-related adverse event at 45.2 percent, with only 7.7 percent of patients experiencing a grade 3 event. “[Although] there has been uncertainty regarding both the efficacy and acceptability of prolonged treatment necessary to reduce recurrence, … the current trial demonstrated that a year of capecitabine was tolerable for most women without significant treatment discontinuation due to toxicity,” the researchers noted.

“The present study result is also consistent with findings from the CREATE-X*** trial, which compared adjuvant capecitabine vs no adjuvant treatment in patients with … hormone receptor-positive tumours as well as women with TNBC, but showed that the TNBC subgroup derived greater benefit from the addition of capecitabine,” they noted. [N Engl J Med 2017;376:2147-2159]

“[In conclusion,] among women with early-stage TNBC who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in [a] significantly improved 5-year DFS,” said the researchers.

*SYSUCC-001: Efficacy of capecitabine metronomic chemotherapy to triple-negative breast cancer

**FinXX, USO01062, and GEICAM-CIBOMA trials

***CREATE-X: Adjuvant capecitabine for breast cancer after preoperative chemotherapy