title: Efficacy and safety of darbepoetin alfa initiated at hemoglobin ≤10 g/dL in patients with stage IV cancer and chemotherapy-induced anemia.
abstract: Data on efficacy and safety of darbepoetin alfa (DA) administered at hemoglobin (Hb) ≤10 g/dL are limited. In this analysis, we examined DA's efficacy and safety in patients with Stage IV cancers and chemotherapy-induced anemia (CIA) initiated on DA at Hb ≤10 g/dL. Data for patients with Stage IV cancers and CIA and who initiated DA at Hb ≤10 g/dL were extracted from three phase 3 trials identified in a central database of Amgen-sponsored DA studies in CIA. Efficacy outcomes were assessed by achievement of Hb increases of ≥1 g/dL and ≥2 g/dL and red blood cell (RBC) or whole blood transfusion requirements. Data were analyzed for all patients with baseline Hb ≤10 g/dL, and by the subgroups of patients with baseline Hb ≥9 to ≤10 g/dL versus <9 g/dL. Crude and Kaplan-Meier proportions of patients who experienced each outcome and time (days) to each outcome were summarized by treatment. Meta-analysis (fixed-effects inverse-variance model) was performed to compare outcomes for DA versus placebo. Safety was assessed by occurrence of adverse events. Data from 213 patients were analyzed: DA, n = 115; placebo, n = 98. More patients in the DA versus the placebo subgroup achieved Hb increase of ≥1 g/dL (72% vs. 36%; HR: 2.92, 95% CI: 1.95, 4.39) and ≥2 g/dL (44% vs. 18%; HR: 2.98, 95% CI: 1.71, 5.21) during the first 12 treatment weeks. Median times to Hb increase of ≥1 g/dL and ≥2 g/dL were 36 days and 78 days for DA, respectively. RBC or whole blood transfusions were less common in patients in the DA versus the placebo subgroup (24% vs. 45%; HR: 0.44, 95% CI: 0.27, 0.73). No new safety issues were reported. Our results confirm that DA use in patients with Stage IV cancer and CIA is more effective than placebo at increasing Hb levels and at reducing transfusion needs when DA treatment is initiated at Hb ≤10 g/dL.
authors.affiliation: Center for Cancer and Blood Disorders, Bethesda, Maryland.
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Boccia
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David H
authors.initials: DH
authors.lastname: Henry
authors.affiliation: LB Biostatistics, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Belton
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Chet
authors.initials: C
authors.lastname: Bohac
authors.affiliation: Kentucky Cancer Clinic, Hazard, Kentucky.
authors.forename: Hassan H
authors.initials: HH
authors.lastname: Ghazal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D000068256:Darbepoetin alfa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004909:Erythrocyte Indices; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006397:Hematinics; D000068256:Darbepoetin alfa
keywords: Chemotherapy-induced anemia; darbepoetin alfa; hemoglobin; meta-analysis