Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebo-controlled trials.
OBJECTIVE
To determine the effect of darbepoetin alfa (DA) on progression-free survival (PFS) and overall survival (OS) in patients with chemotherapy-induced anemia (CIA).


METHODS
Two 16-week randomized, double-blind, placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer (n = 314) or lymphoproliferative malignancies (LPMs; n = 344) undergoing chemotherapy were analyzed with prospectively defined long-term PFS and OS end points. Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding, double-blind, placebo-controlled studies in anemic patients with multiple tumor types (n = 405) and LPMs (n = 66).


RESULTS
Median follow-up is 15.8 months (lung cancer) and 32.6 months (LPM). Median duration of PFS was comparable between DA and placebo: 5.1 months (95% CI, 4.1 to 6.9 months) versus 4.4 months (95% CI, 3.7 to 5.3 months) for lung cancer and 14.2 months (95% CI, 12.2 to 17.5 months) versus 15.9 months (95% CI, 13.1 to 19.0 months) for LPMs. The estimated hazard ratio (HR) of death related to DA use for lung cancer was 0.77 (95% CI, 0.59 to 1.01) and 1.26 (95% CI, 0.92 to 1.71) for LPMs. In the pooled analyses of all four studies (n = 1,129), no differences in PFS or OS were observed between DA and placebo (HR = 0.92; 95% CI, 0.78 to 1.07; and HR = 0.95; 95% CI, 0.78 to 1.16, respectively).


CONCLUSIONS
Treatment with DA does not seem to influence PFS or OS in patients with CIA. Prospective, randomized clinical trials will provide additional insights into the effects of DA on PFS and OS in specific tumor types.
Hedenus
Michael
M
Department of Internal Medicine, Sundsvall Hospital, Sundsvall S-851 86, Sweden. Michael.Hedenus@lvn.se
Vansteenkiste
Johan
J
Kotasek
Dusan
D
Austin
Matthew
M
Amado
Rafael G
RG
D000740:Anemia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D000068256:Darbepoetin alfa; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D010919:Placebos; D016019:Survival Analysis; D016896:Treatment Outcome
D010919:Placebos; D004921:Erythropoietin; D000068256:Darbepoetin alfa