DEVA: Randomized trial of sequential epirubicin and docetaxel versus epirubicin alone in node-positive postmenopausal early breast cancer (EBC) patients.

Abstract

536 Background: This group previously showed that fractionated epirubicin (EPI) alone is an active, well tolerated adjuvant regimen in postmenopausal women (Wils, JCO, 1999). DEVA evaluated the efficacy and toxicity of incorporating docetaxel (DOC) to create a sequential anthracycline-taxane regimen. Methods: Following complete tumour excision, postmenopausal women with node-positive EBC were randomised to either EPI 50 mg/m2 d1 and 8 every 4 weeks for 6 cycles, or EPI-DOC 3 cycles EPI (as above) then 3 cycles of docetaxel 100 mg/m2 d1 every 3 weeks. Patients with ER positive EBC also received endocrine therapy for 5 years. Disease-free survival (DFS) (local and distant relapse, 2nd primary breast cancer, intercurrent death) and overall survival (OS) were evaluated. Results: From 1997 to 2005, 803 patients at 36 centres entered DEVA (EPI n = 397, EPI-DOC n = 406). 198 DFS events have been reported (EPI-DOC n = 84 EPI n = 114); median follow-up 64.7 months (IQR 45.2-84.4 months). 5-year DFS rates were EPI-DOC 79.5% (CI 75.2-83.8) and EPI 72.7% (CI 68.0-77.3) with evidence of improvement in DFS with EPI-DOC (HR = 0.68; 95% CI 0.52-0.91; p = 0.008). Adjustment for factors known to affect prognosis (ER status, grade, tumour size, extent of node involvement) slightly increased size of DFS effect (HR = 0.58; 95% CI 0.43-0.79) with no evidence of a differential effect within the subgroups. 127 patients have died (EPI-DOC 52, EPI 75) with a reduction in deaths with EPI-DOC (HR = 0.66; CI 0.46-0.94; p = 0.02). 5-year OS rates were EPI-DOC 88.9 (CI 85.5-92.2) and EPI 81.8 (CI 77.7-85.9). 20 patients (EPI-DOC n = 7 EPI n = 13) died with no evidence of breast cancer relapse; 6 were due to cardiac disease (EPI-DOC n = 1 EPI n = 5). From cycles 4-6 onwards, with exception of nausea/vomiting (p = 0.003), EPI-DOC was more toxic than EPI including infection (p = 0.001), febrile neutropenia, myalgia, peripheral neuropathy, oedema, skin and nail abnormalities, and stomatitis (all p < 0.001). Conclusions: These mature results suggest, within a relatively small trial, that substitution of docetaxel for epirubicin for the last three cycles of chemotherapy results in improved outcome in postmenopausal, node-positive EBC patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Pfizer, sanofi-aventis Pfizer