Randomized comparison of every-2-week darbepoetin alfa and weekly epoetin alfa for the treatment of chemotherapy-induced anemia: The 20030125 study group trial

Purpose Chemotherapy-induced anemia is widely treated in the United States with darbepoetin alfa (DA) or epoetin alfa (EA). This noninferiority study systematically compares efficacy and safety of DA and EA using common doses and schedules used in clinical practice. Methods Patients had a diagnosis of nonmyeloid malignancy with >= 8 weeks of planned chemotherapy, age >= 18 years, and anemia (hemoglobin <= 11 g/dL). Patients were randomly assigned 1:1 to DA 200 mu g every two weeks (Q2W) or EA 40,000 units every week (QW) for up to 16 weeks with identical dose adjustment rules. Efficacy was assessed by the incidence of RBC transfusion (Kaplan-Meier estimate). The definition of noninferiority was that the upper 95% Cl limit of the observed difference in RBC transfusions between groups was less than 11.5%; this noninferiority margin was based on the treatment effect observed in placebo-control led EA studies. Results Of 1,220 patients randomly assigned, 1,209 received >= one dose of the study drug. Common tumor types were lung (26%), breast (21 %), and gastrointestinal (18%). Transfusion incidence from week 5 to the end of the treatment phase (the primary end point) was 21 % in the DA group and 16% in the EA group; noninferiority was concluded because the upper 95% Cl limit of the difference between groups (10.8%) was below the prespecified noninferiority margin. Sensitivity analyses using alternate statistical methods and analysis sets yielded similar results. Hemoglobin, quality of life, and safety end points further support equivalency of the erythropoietic therapies. Conclusion This large, phase III study demonstrates comparable efficacy of DA Q2W and EA QW. Less frequent dosing offers potential benefits for patients, caregivers and health care providers.