Effectiveness of Darbepoetin Alfa for Chemotherapy-induced Anemia When Initiated at Hemoglobin ≤10 g/dL

Purpose: 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. Findings: 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. Implications: 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. (C) 2016 The Authors. Published by Elsevier HS Journals, Inc.