Capecitabine is approved for the treatment of advanced breast cancer, but not for adjuvant treatment of early breast cancer. The randomised FinXX trial evaluated the addition of capecitabine to an adjuvant chemotherapy regimen consisting of docetaxel, followed by cyclophosphamide, epirubicin, and fluorouracil. After a median follow-up of 15 years, the capecitabine-containing regimen significantly improved overall survival compared with docetaxel-cyclophosphamide and epirubicin plus fluorouracil.
Adjuvant chemotherapy improves overall survival (OS) of patients with early breast cancer, but the benefit depends on the type and intensity of chemotherapy. Capecitabine is an oral prodrug of fluorouracil, approved for the treatment of advanced breast cancer but not for the (neo)adjuvant treatment of early breast cancer. Recent findings indicate that the addition of capecitabine to standard adjuvant chemotherapy prolongs disease-free survival. In preclinical models, agents such as docetaxel, paclitaxel, and cyclophosphamide increase cancer thymidine phosphorylase concentration. This potentially leads to improved conversion of capecitabine to fluorouracil within the tumour, suggesting that concomitant administration of capecitabine with such drugs improves efficacy compared with single-agent capecitabine. The randomised FinXX trial evaluated the addition of capecitabine (X) to an adjuvant chemotherapy regimen consisting of docetaxel (T), followed by cyclophosphamide (C), epirubicin (E), and fluorouracil (F).
The Finland Capecitabine Trial (FinXX) is a randomised, open-label, multicentre trial that evaluates the integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Eligible patients had to be adults with invasive breast cancer, had a WHO performance status < 2 and a time interval between breast surgery and the date of random assignment ≤ 12 weeks. The axillary lymph nodes were required to contain cancer (pN-positive), or when cancer was node-negative (pN0), the tumour diameter had to be ≥ 20 mm and cancer progesterone receptor (PR) expression-negative. No distant metastases were allowed in the staging examinations. The patients were randomly allocated (1:1) to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin and capecitabine (CEX), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF).
A total of 1,500 patients were accrued between January 2004 and May 2007 and randomly assigned to either the capecitabine arm (TX-CEX) or the control arm (T-CEF). After five patients were excluded from the intention-to-treat population, the TX-CEX and the T-CEF group comprised 751 and 744 patients, respectively. Most patients (76.4%) had ER-positive cancer, and 18.9% had HER-2 positive cancer. The data collection for OS was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years in the TX-CEX group and 15.4 years in the T-CEF group. During this period, 25.1% of the patients died: 171 (22.8%) in the TX-CEX group and 204 (27.4%) in the T-CEF group. OS was significantly longer in the TX-CEX group compared to the T-CEF group (HR[95%CI]: 0.81[0.66-0.99], p= 0.037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group.
Furthermore, subgroup analyses revealed that patients with ER-negative cancer and those with HER2-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF. When four subgroups were formed using cancer steroid hormone receptor status (ER-positive and/or PR-positive vs. ER-negative and PR-negative) and HER2 status (positive vs. negative), patients with triple-negative cancer (TNBC) tended to survive longer when treated with TX-CEX, whereas little survival benefit was observed in the three other subgroups. However, no significant interactions were detected between the study treatments and the subgroups.
During a median patient follow-up time of fifteen years, the addition of capecitabine to a chemotherapy regimen that included docetaxel, cyclophosphamide, and epirubicin improved OS in patients with early breast cancer. These results suggest that adjuvant capecitabine-containing chemotherapy could be considered for some patients with early breast cancer. In predefined subgroup analyses, patients with ER-negative cancer, HER2-negative cancer, and TNBC tended to benefit most from capecitabine-containing chemotherapy, but the subgroup analyses need to be interpreted with caution.