Publication

Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast cancer: randomized clinical trial

Journal Paper/Review - Jul 16, 2013

Units
PubMed
Doi

Citation
Moebus V, Untch M, Kreienberg R, Hinke A, Runnebaum I, Nitz U, Kuhn W, Kurbacher C, Thomssen C, du Bois A, Lueck H, Huober J, Schneeweiss A, Jackisch C, AGO Breast Study Group. Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast cancer: randomized clinical trial. J Natl Cancer Inst 2013; 105:1018-26.
Type
Journal Paper/Review (English)
Journal
J Natl Cancer Inst 2013; 105
Publication Date
Jul 16, 2013
Issn Electronic
1460-2105
Pages
1018-26
Brief description/objective

BACKGROUND
The AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel (EC→T) (every 3 weeks) as adjuvant treatment in high-risk breast cancer patients. The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second randomization of the intense dose-dense arm.

METHODS
One thousand two hundred eighty-four patients were enrolled; 658 patients were randomly assigned to the IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further randomly assigned to the epoetin alfa group, and 319 were randomly assigned to the non-erythropoiesis-stimulating agent (ESA) control group. Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion. Relapse-free survival, overall survival, and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods. Except for the primary hypothesis, all statistical tests were two-sided.

RESULTS
Epoetin alfa avoided the decrease in hemoglobin level (no decrease in the epoetin alfa group vs -2.20g/dL change for the control group; P < .001) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs 28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse.

CONCLUSIONS
Epoetin alfa resulted in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival. However, epoetin alfa had an adverse effect, resulting in increased thrombosis.