Randomized phase III study of adjuvant chemotherapy for node-positive early breast cancer (BC) patients (pts) comparing epirubicin plus cyclophosphamide followed by docetaxel (EC-T) versus epirubicin plus docetaxel followed by capecitabine (ET-X): Efficacy analysis of the GEICAM/2003-10 trial.

Abstract

1027 Background: X is an active drug in metastatic breast cancer. GEICAM/2003-10 is an adjuvant trial investigating the integration of capecitabine into an epirubicin and docetaxel containing regimen for node-positive early breast cancer pts. Methods: Pts aged 18-70, with T1-T3/N1-3 operable BC were eligible. HER2+ pts were initially allowed. In October 2005, after 803 pts were included in the trial, the study was amended to exclude them. Pts were stratified by site, menopausal status, number of axillary nodes (1-3, 4-9, >9) and hormonal receptor status and randomized to receive EC (90/600 mg/m2 x4) followed by T (100 mg/m2 x4) or ET (90/75 mg/m2 x4) followed by X (1,250 mg/m2 BID, d1–14, x 4) all every three weeks. The primary endpoint was DFS. The trial was designed to detect an absolute 5-y DFS increase of 7% (72% EC-T, 79% ET-X); a sample size of 1,184 evaluable pts (592 per arm) was required to detect this difference (a=0.05, β=80%). Assuming a drop-out rate of 17%, 1,382 pts were required. The first analysis of DFS was planned after 290 events. Results: Between February 2004 and February 2007, 1384 pts (EC-T 669, ET-X 715) were randomized. Patient characteristics were balanced between arms, median age was 51, 84% of pts were HR positive and 11% HER2 positive; 66, 25 and 9% had 1-3, 4-9 and > 9 nodes respectively. The median relative dose intensity was 99% for EC, 99% for T, 99% for ET and 94% for X. The most frequent grade 3-4 toxicities (>5% in either arm) with EC-T vs. ET-X were neutropenia (19% vs. 10%) with 7% febrile neutropenia in both arms, hand-foot syndrome (2% vs. 20%), fatigue (13% vs. 11%), diarrhea (3% vs. 11%), stomatitis (6% vs. 5%) and vomiting (5% vs. 5%). After a median follow-up of 6.6 years and 292 events, the proportion of patients disease free at 5 years is 86% and 82% with EC-T and ET-X (HR for relapse 1.314, 95% CI: 1.042 – 1.657); log-rank p-value=0.0208. Overall survival was not different between treatment arms (HR 1.113, 95% CI: 0.809 – 1.531); log rank p-value=0.511. Conclusions: DFS has been in favour of EC-T in pts with node-positive early BC. Clinical trial information: NCT00129935.