The Finland Capecitabine Trial (FinXX) researchers found that addition of capecitabine to a taxane-anthracycline chemotherapy backbone improved overall survival (OS) in patients with early breast cancer during a median follow-up for approximately 15 years after the date of random assignment. The improvement in OS was statistically significant, but modest. In predefined subgroup analyses, patients with oestrogen receptor (ER)-negative cancer, HER2-negative cancer, and triple negative breast cancer (TNBC) tended to benefit most from capecitabine-containing chemotherapy, but the subgroup analyses need to be interpreted with caution. Prof. Heikki Joensuu of the Department of Oncology, Helsinki University Hospital and University of Helsinki in Helsinki, Finland and colleagues published the study findings on 12 January 2021 in the Journal of Clinical Oncology.

The authors wrote in the study background that capecitabine is an oral prodrug of fluorouracil that is approved for the treatment of advanced breast cancer, but not for neoadjuvant or adjuvant treatment of early breast cancer. Several randomised studies have evaluated capecitabine as neoadjuvant or adjuvant treatment of early breast cancer. In some of these studies, capecitabine was added to the chemotherapy backbone, whereas in others a chemotherapy agent was replaced by capecitabine in the experimental arm. 

A recent meta-analysis of randomised studies on the basis of individual patient data found that addition of capecitabine to standard adjuvant chemotherapy regimens prolongs disease-free survival, whereas replacing a standard agent with capecitabine did not improve it.

In preclinical models, agents such as docetaxel, paclitaxel, and cyclophosphamide increase cancer thymidine phosphorylase concentration potentially leading 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 FinXX is a randomised, open-label, multicentre study that evaluated integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 2004 and May 2007, a total of 1500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued.

The patients were randomly allocated to either TX-CEX regimen (753 patients), consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX), or to T-CEF (747 patients), consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF).

A protocol-scheduled analysis of OS was performed on the basis of approximately 15-year follow-up of the patients. The data collection was locked on 31 December 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.

Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% confidence interval [CI] 0.66 to 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.

In exploratory subgroup analyses, patients with ER–negative cancer and those with TNBC treated with TX-CEX tended to live longer than those treated with T-CEF.

The authors commented that the current report is based on the longest follow-up time of the randomised studies evaluating either neoadjuvant or adjuvant capecitabine in patients with breast cancer. The findings suggest that addition of capecitabine to a taxane-anthracycline chemotherapy backbone improves OS and that adjuvant capecitabine-containing chemotherapy could be considered as an option for some patients with early breast cancer.

The study was supported by Roche, Sanofi, and AstraZeneca. It was also supported by the Cancer Society of Finland, Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation, Academy of Finland, and Research Funds of Helsinki University Hospital.


Joensuu H, Kellokumpu-Lehtinen P-L, Huovinen R, et al. Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial. JCO; Published online 12 January 2022. DOI: 10.1200/JCO.21.02054