TY - JOUR
T1 - Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer
T2 - a meta-analysis of randomised trials
AU - Bohlius, Julia
AU - Schmidlin, Kurt
AU - Brillant, Corinne
AU - Schwarzer, Guido
AU - Trelle, Sven
AU - Seidenfeld, Jerome
AU - Zwahlen, Marcel
AU - Clarke, Michael
AU - Weingart, Olaf
AU - Kluge, Sabine
AU - Piper, Margaret
AU - Rades, Dirk
AU - Steensma, David P.
AU - Djulbegovic, Benjamin
AU - Fey, Martin F.
AU - Ray-Coquard, Isabelle
AU - Machtay, Mitchell
AU - Moebus, Volker
AU - Thomas, Gillian
AU - Untch, Michael
AU - Schumacher, Martin
AU - Egger, Matthias
AU - Engert, Andreas
N1 - Funding Information:
JB received honoraria and travel grants from Amgen. AE received research funding and honoraria from Amgen, Roche, and Johnson & Johnson. GT received research funding for the GOG-191 study by Johnson & Johnson. BD received research funding from OrthoBiotech and consulted for Amgen. MM received honoraria from OrthoBiotech. VM received research funding and honoraria from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, and Roche. MU received research funding for the PREPARE study from Amgen and Bristol-Myers Squibb. MP is employed by the Blue Cross and Blue Shield Association, the trade organisation for the independent US Blue Cross Blue Shield health insurance plans, but is not involved in the determination of coverage and reimbursement policy for individual plans. The other researchers declare that they have no conflicts of interest.
Funding Information:
This project was funded by the German Federal Ministry of Education and Research (grant 01KG0611), Medical Faculty of University of Cologne, Cologne, Germany, and Oncosuisse, Bern, Switzerland (grant OCS-02146-10-2007). We thank Ina Monsef and Frauke Naumann for help with literature searches and Nicole Skoetz for technical assistance; John Spivak and Pia Raanani for review of the protocol, and Stuart Pocock and Sue Richard for critical review of a previous version of this report; Jens Blohmer for providing unpublished study results; and the companies that contributed study data.
PY - 2009
Y1 - 2009
N2 - Background: Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer. Methods: Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups. Findings: Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1·17, 95% CI 1·06-1·30) and worsened overall survival (1·06, 1·00-1·12), with little heterogeneity between trials (I2 0%, p=0·87 for mortality during the active study period, and I2 7·1%, p=0·33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1·10 (0·98-1·24), and 1·04 (0·97-1·11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0·42). Interpretation: Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits. Funding: German Federal Ministry of Education and Research, Medical Faculty of University of Cologne, and Oncosuisse (Switzerland).
AB - Background: Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer. Methods: Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups. Findings: Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1·17, 95% CI 1·06-1·30) and worsened overall survival (1·06, 1·00-1·12), with little heterogeneity between trials (I2 0%, p=0·87 for mortality during the active study period, and I2 7·1%, p=0·33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1·10 (0·98-1·24), and 1·04 (0·97-1·11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0·42). Interpretation: Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits. Funding: German Federal Ministry of Education and Research, Medical Faculty of University of Cologne, and Oncosuisse (Switzerland).
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U2 - 10.1016/S0140-6736(09)60502-X
DO - 10.1016/S0140-6736(09)60502-X
M3 - Article
C2 - 19410717
AN - SCOPUS:65449117261
SN - 0140-6736
VL - 373
SP - 1532
EP - 1542
JO - The Lancet
JF - The Lancet
IS - 9674
ER -
