JAMA Oncol
Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer: The Randomized Clinical FinXX Trial.
Abstract
Importance
Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC).
Objective
To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2).
Design, setting, and participants
This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015.
Main outcomes and measures
Recurrence-free survival (RFS).
Results
Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively).
Conclusions and relevance
Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis.
Trial registration
clinicaltrials.gov Identifier: NCT00114816.
Related Questions
Would you consider adjuvant capecitabine for a patient with triple-negative metaplastic carcinoma who has microinvasive residual disease (ypT1miN0) following neoadjuvant therapy?
For a patient with triple-negative metaplastic breast cancer and microinvasive residual disease (ypT1miN0)following neoadjuvant therapy, the decision to use adjuvant capecitabine is nuanced and not definitively addressed in current guidelines or trials. General TNBC with Residual Disease: Multiple...
Is there a role for adjuvant capecitabine in sequence with abemaciclib for high risk HR+ breast cancer with residual disease?
Several randomized trials and meta-analyses have failed to show the benefit of adding capecitabine in Neo-adjuvant or adjuvant setting, except for selected TNBC patients. GEICAM/2003-10 and FinXX are few of those well-conducted studies that explored the addition of capecitabine in early stage breast...
Can 5-FU be substituted for adjuvant capecitabine for a dialysis dependent patient with triple negative breast cancer s/p neoadjuvant chemotherapy followed by mastectomy showing small residual disease?
I would not substitute 5-FU in this situation.Although the CREATE-X trial showed a survival benefit for adjuvant capecitabine in women who do not achieve pCR with neoadjuvant chemotherapy in a subset analysis of women with triple negative breast cancer, there are reasons to be concerned about these ...