title: Effectiveness of Darbepoetin Alfa for Chemotherapy-induced Anemia When Initiated at Hemoglobin ≤10 g/dL.
abstract: OBJECTIVE
  Limited data are available to describe the effectiveness of darbepoetin alfa (DA) in terms of hemoglobin (Hb) and transfusion outcomes when initiated at Hb ≤10 g/dL (the threshold specified in the summary of prescribing characteristics). We assessed DA, initiated according to current labeling (Hb ≤10 g/dL), in chemotherapy-induced anemia (CIA).
  
  
  METHODS
  Data for patients with cancer and CIA who initiated DA at Hb ≤10 g/dL were extracted from a database of Amgen-sponsored trials. A comparative analysis was limited to randomized, controlled trials in patients treated with DA or control (placebo/best supportive care). Data for the DA arm(s) of randomized, multiple-arm, or prospective, single-arm trials were also extracted (DA-only analysis; non-front-loaded studies only). Outcomes included Hb increase ≥1 g/dL or ≥2 g/dL during the first 12 weeks of treatment. Crude and Kaplan-Meier proportions of patients who experienced each outcome and time (days) to each outcome were summarized by treatment arm. Meta-analysis (fixed-effects inverse-variance method) was performed to compare outcomes for DA with control.
  
  
  RESULTS
  The comparative analysis included 4 studies (2 in lung cancer, 1 in lymphoproliferative disease, and 1 in non-myeloid malignancy: DA, n = 261; control, n = 273). The DA-only analysis included 15 studies (n = 3768). In comparative analyses, more patients who received DA than placebo achieved Hb increase of ≥1 g/dL (fixed-effects hazard ratio [HR] = 2.07; 95% CI, 1.62-2.63) or ≥2 g/dL (HR = 2.91; 95% CI, 2.09-4.06). Median times to ≥1 g/dL or ≥2 g/dL increase were 43 or 78 days for DA (not evaluable for placebo). Transfusions were less common in patients who received DA (HR = 0.58; 95% CI, 0.44-0.77). Addition of 2 dose-finding studies did not change the findings of the main comparative analysis. Results were similar in the DA-only analyses.
  
  
  CONCLUSIONS
  This is the first patient-level meta-analysis, to our knowledge, to evaluate the efficacy in terms of Hb response of DA treatment when initiated according to current product labeling in patients with CIA. Limitations include the small number of studies and patients eligible for inclusion in the comparative analyses and the absence of non-Amgen trials of DA. The results of the comparative analysis confirm that DA is more effective than placebo at increasing serum Hb levels and at reducing the need for transfusion in patients with CIA when treatment is initiated at Hb ≤10 g/dL, as per current product labeling.
authors.affiliation: Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. Electronic address: robert.pirker@meduniwien.ac.at.
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
authors.affiliation: Department of Medicine, Sundsvall Hospital, Sundsvall, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Hedenus
authors.affiliation: Respiratory Oncology Unit (Pulmonology), University Hospital Ku Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.affiliation: Obstetrics, Gynecology and Reproductive Sciences, Temple University Hospital, Philadelphia, Pennsylvania.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernandez
authors.affiliation: Biostatistics, Amgen Limited, Uxbridge, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Belton
authors.affiliation: Medical, Amgen Switzerland AG, Zug, Switzerland.
authors.forename: Jan-Henrik
authors.initials: JH
authors.lastname: Terwey
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy* / Q000628:therapy; D000970:Antineoplastic Agents / Q000009:adverse effects; D001803:Blood Transfusion; D000068256:Darbepoetin alfa / Q000627:therapeutic use*; D016208:Databases, Factual; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D006397:Hematinics; D006454:Hemoglobins; D010919:Placebos; D000068256:Darbepoetin alfa
keywords: chemotherapy-induced anemia; darbepoetin alfa; hemoglobin; licensed indication; meta-analysis; transfusion