Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast cancer: randomized clinical trial
Moebus V, Jackisch C, Schneeweiss A, Huober J, Lueck HJ, du Bois A, Thomssen C, Kurbacher C, Kuhn W, Nitz U, et al
Journal of the National Cancer Institute. 2013;105((14):):1018-26.
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.
Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials
Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke M, Weingart O, Kluge S, et al
Erythropoietin or darbepoetin for patients with cancer - meta-analysis based on individual patient data
Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke MJ, Weingart O, Kluge S, et al
Cochrane Database of Systematic Reviews. 2009;((3):):CD007303.
Effect of once-weekly epoetin beta on survival in patients with metastatic breast cancer receiving anthracycline- and/or taxane-based chemotherapy: results of the Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study
Aapro M, Leonard RC, Barnadas A, Marangolo M, Untch M, Malamos N, Mayordomo J, Reichert D, Pedrini JL, Ukarma L, et al
Journal of Thrombosis and Haemostasis. 2008;26((4):):592-8.
PURPOSE The Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study evaluated whether epoetin beta would improve survival in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS BRAVE was an open-label, randomized, multicenter study in patients with MBC treated with anthracycline- and/or taxane-based chemotherapy. Patients (hemoglobin [Hb] < 12. 9 g/dL) were randomly assigned (1:1) to epoetin beta 30,000 U subcutaneously once weekly or control for 24 weeks. The primary efficacy variable was overall survival. Secondary efficacy outcomes included progression-free survival, transfusion- and severe anemia-free survival, Hb response, safety, and quality of life (QoL). RESULTS After 18 months of follow-up, 62 (27%) of 231 patients survived with epoetin beta therapy and 63 (27%) of 232 with control. No difference was detected in overall survival (hazard ratio [HR] = 1. 07; 95% CI, 0. 87 to 1. 33, P = . 522) or progression-free survival (HR = 1. 07; 95% CI, 0. 89 to 1. 30, P = . 448). There was a statistically significant benefit on transfusion- and severe anemia-free survival compared with control (HR = 0. 59; P = . 0097). Median Hb level increased with epoetin beta (11. 7 g/dL at baseline to 13. 3 g/dL at 24 weeks) but did not change with control (11. 5 v 11. 4 g/dL). Patients receiving epoetin beta experienced more thromboembolic events (TEEs) compared with controls (13% v 6%; P = . 012) with no difference in serious TEEs (4% v 3%). Epoetin beta did not significantly improve QoL in this study where patients had a high baseline Hb value. CONCLUSION In patients with MBC receiving chemotherapy and initial Hb less than 12. 9 g/dL, epoetin beta increased Hb. No difference was detected in overall survival. Because of its superiority design, this study cannot, however, exclude clinically important differences in survival with absolute certainty.
Recombinant human erythropoiesis stimulating agents in cancer patients: individual patient data meta-analysis on behalf of the EPO IPD Meta-Analysis Collaborative Group
Bohlius J, Brillant C, Clarke M, Kluge S, Napoli M, Piper M, Rades Dirk, Ray-Coquard I, Schmidlin K, Schumacher M, et al
Blood. 2008;112((11):): Abstract No. 6 & Abstract No. 4675