More to Be Gained with Capecitabine in Breast Cancer?

Optimizing adjuvant therapy to reduce risk for recurrence has been a quest for decades, particularly in patients with higher risk triple-negative breast cancer (TNBC). A recent meta-analysis demonstrated that in patients with higher risk, early-stage TNBC, the addition of pembrolizumab to neoadjuvant chemotherapy improved pathologic complete response and prolonged event-free survival (Cancer Res 2020; 80 suppl 4; abstr GS1-07). The CREATE-X trial demonstrated that the addition of postoperative capecitabine, particularly in patients with TNBC who had residual disease following neoadjuvant therapy, further reduced risk of recurrence (NEJM JW Oncol Hematol Aug 2017 and N Engl J Med 2017; 376:2147). One of the first trials to evaluate the addition of capecitabine to standard chemotherapy was the Finland Capecitabine Trial (Fin XX), and now, investigators report 15-year overall survival results.

In Fin XX, 1500 patients with axillary node–positive or high-risk, axillary node–negative breast cancer were randomized to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (T-CEF) or to three cycles of docetaxel with capecitabine followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (TX-CEX). In patients with ER-positive tumors, adjuvant endocrine therapy was initiated within 2 months after completion of chemotherapy. Median age was 53 years, 76% of patients were ER-positive, 19% were HER2-positive, 13% had TNBC, >90% had T1 or T2 tumors, and 89% were node positive.

Survival at 5, 10, and 15 years favored the regimen containing capecitabine; 15-year survival was 77.6% in the TX-CEX group versus 73.3% in the T-CEF group (hazard ratio, 0.81; P=0.037). Exploratory subgroup analysis suggested that patients with ER-negative disease and those with TNBC lived longer with the addition of capecitabine.