Adjuvant Capecitabine for Early Breast Cancer

15-Year Overall Survival Results From a Randomized Trial

Heikki Joensuu, MD; Pirkko-Liisa Kellokumpu-Lehtinen, MD; Riikka Huovinen, MD; Arja Jukkola, MD; Minna Tanner, MD; Johan Ahlgren, MD; Päivi Auvinen, MD; Outi Lahdenperä, MD; Kenneth Villman, MD; Paul Nyandoto, MD; Greger Nilsson, MD; Paula Poikonen-Saksela, MD; Vesa Kataja, MD; Petri Bono, MD; Jouni Junnila, MSc; Henrik Lindman, MD


J Clin Oncol. 2022;40(10):1051-1058. 

In This Article

Abstract and Introduction


Purpose: Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer.

Methods: The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients.

Results: The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5–16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8–16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .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 estrogen receptor–negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF.

Conclusion: Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.


Adjuvant chemotherapy improves overall survival (OS) of patients with early breast cancer, but the benefit is dependent on the type of chemotherapy administered and chemotherapy dose intensity.[1,2]

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 randomized studies have evaluated capecitabine as neoadjuvant[3–7] or adjuvant[8–17] treatment of early breast cancer. In some of these studies, capecitabine was added to the chemotherapy backbone,[4,7,10,12,13,16,17] whereas in others a chemotherapy agent was replaced by capecitabine in the experimental arm.[3,8,9,11,14,15] A recent meta-analysis of randomized trials 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 disease-free survival.[18] 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 tumor, suggesting that concomitant administration of capecitabine with such drugs improves efficacy compared with single-agent capecitabine.[19,20]

The main purpose of adjuvant treatment is to prolong OS. Breast cancer may recur late, but little long-term OS data are available from the trials that have evaluated capecitabine in the treatment of early breast cancer. We report here the OS results of the randomized Finland Capecitabine Trial (FinXX) during a median patient follow-up time of approximately 15 years since the date of random assignment. To the best of our knowledge, the current results are based on the longest follow-up time reported from the adjuvant or neoadjuvant capecitabine trials addressing breast cancer. The 15-year analysis of OS was scheduled in the FinXX Study Protocol (online only). The findings suggest that addition of capecitabine to a taxane-anthracycline chemotherapy backbone improves OS of the patients.