title: Pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials of darbepoetin alfa in the treatment of patients with chemotherapy-induced anemia.
abstract: OBJECTIVE
  Although numerous clinical trials have demonstrated the efficacy and tolerability of erythropoiesis-stimulating agents (ESAs) in patients with chemotherapy-induced anemia (CIA), results of some recent trials and one meta-analysis have suggested that ESAs may negatively impact survival and/or disease control in patients with cancer.
  
  
  METHODS
  To assess the benefits and risks of ESAs in CIA, we conducted a pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials in 2,122 patients with CIA receiving darbepoetin alfa (DA; n = 1,200) or placebo (n = 912).
  
  
  RESULTS
  DA did not increase mortality (hazard ratio = 0.97; 95% CI, 0.85 to 1.1) and had no effect on progression-free survival (hazard ratio = 0.93; 95% CI, 0.84 to 1.04) and disease progression (hazard ratio = 0.92; 95% CI, 0.82 to 1.03), but, as expected, increased the risk for thromboembolic events (hazard ratio = 1.57; 95% CI, 1.10 to 2.26). Overall and progression-free survival were not affected by baseline hemoglobin and seemed better in patients who achieved hemoglobin more than 12 or more than 13 g/dL. Transfusions and rates of hemoglobin increase (> 1 g/dL in 14 days; > 2 g/dL in 28 days) owing to transfusions were associated with an increased risk for death and disease progression in both treatment groups; in the absence of transfusions, rates of hemoglobin increase did not appear to increase the risk for adverse outcomes. Compared with placebo, DA significantly reduced the risk of receiving one or more transfusion.
  
  
  CONCLUSIONS
  There seemed to be no association between DA and risk of death or disease progression in this meta-analysis of individual patient data from DA studies conducted in CIA, the approved indication for ESAs in oncology.
authors.affiliation: Wilhelminenspital, Department of Medicine I, Center for Oncology and Hematology, Pavillion 23, Montleartstrasse 37, Vienna 1160, Austria. heinz.ludwig@wienkav.at
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: David H
authors.initials: DH
authors.lastname: Henry
authors.forename: Alex
authors.initials: A
authors.lastname: Fleishman
authors.forename: Ken
authors.initials: K
authors.lastname: Bridges
authors.forename: John A
authors.initials: JA
authors.lastname: Glaspy
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects; D001804:Blood Transfusion, Autologous; D002986:Clinical Trials as Topic; D000068256:Darbepoetin alfa; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa