Objective: To evaluate if a darbepoetin alfa correction/maintenance dosing regimen is non-inferior to a weekly regimen with respect to red blood cell transfusion requirements in patients with chemotherapy-induced anemia (CIA).
Research design and methods: In this randomized, active-controlled, double-blind phase 3 trial, CIA patients were randomized 1:1 to receive darbepoetin alfa in either a correction/maintenance schedule (4.5 microg/kg weekly for 4 weeks followed by 4.5 microg/kg every 3 weeks (Q3W)) or a weekly schedule (2.25 microg/kg weekly). The primary endpoint was the transfusion incidence during weeks 1-16. Non-inferiority was to be concluded if the upper limit of the 95% confidence interval (CI) of the difference in transfusion incidence between treatment groups was below 12.5%. Hematologic responses and safety profiles were also compared.
Results: Transfusion incidence (95% CI) during weeks 1-16 was 37% (32-42) and 38% (32-43) in the weekly and correction/maintenance groups, respectively. The difference (95% CI) in transfusions was 0.4% (-7.0 to 7.8), demonstrating non-inferiority between treatment groups. Similar percentages in both groups achieved and maintained hemoglobin in a target range of 11-13 g/dL and had clinically meaningful FACT-F score improvements. The median (range) time to hemoglobin response was 10 (1-17) weeks and 12 (2-17) weeks in the weekly and correction/maintenance groups, respectively. Both groups had similar safety profiles.
Conclusions: A correction/maintenance schedule with its initial two-fold higher weekly dosing and subsequent Q3W dosing yielded outcomes similar to those observed with a weekly schedule. Although correction/maintenance dosing provided no incremental clinical benefit, Q3W dosing could provide benefits of convenience and facilitate patient compliance.