Randomized, double-blind, placebo-controlled trial of every-3-week darbepoetin alfa 300 micrograms for treatment of chemotherapy-induced anemia

ABSTRACT

Objective: Darbepoetin alfa is effective in treating chemotherapy-induced anemia (CIA). Administration of subcutaneous darbepoetin alfa every 3 weeks (Q3W) could simplify treatment through synchronization with common Q3W chemotherapy regimens. We report results from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA.

Research design and methods: Patients aged ≥ 18 years with anemia (hemoglobin <11 g/dL) being treated for nonmyeloid malignancy were randomized 1:1 to receive darbepoetin alfa 300 μg (n = 193) or placebo (n = 193) subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be adjusted per prespecified rules.

Main outcome measures: The primary endpoint was the proportion of patients who received ≥1 red blood cell (RBC) transfusion between week 5 and the end of the treatment period (EOTP). The study also analyzed the proportions of patients achieving a hemoglobin concentration ≥11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL, and the change in hemoglobin concentration over time.

Results: The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group (24 vs. 41% of patients, a 16.3% difference, p < 0.001). There were no differences between the two treatment arms in quality-of-life measures. Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels. Study limitations suggest caution in the interpretation of these results: transfusions, the primary endpoint, were recommended but not required if hemoglobin concentrations were ≤8.0 g/dL, and protocol deviations (primarily dosing errors) occurred in approximately one-half of the patients in both treatment groups.

Conclusions: In this study, fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA.

Trial registration: ClinicalTrials.gov identifier: NCT00110955.

Key words: :

• Anemia
• Chemotherapy-induced
• Darbepoetin alfa
• Extended dosing
• Randomized

Transparency

Declaration of funding

This study was funded by Amgen Inc.

Declaration of financial/other relationships

E.H. has disclosed that he has acted as a consultant for Amgen Inc. V.C. has disclosed that she has performed contract work for Amgen Inc. and Johnson & Johnson, and owns stock in Amgen, Genentech, Bristol Myers-Squibb and GlaxoSmithKline. D.T. and T.L. are employees and stockholders of Amgen Inc. All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she is on the speakers’ bureau of Pfizer. The other reviewer has disclosed that he/she has no relevant financial relationships.

Acknowledgment

The authors thank all of the investigators, coordinators and patients in the ARANESP 20030232 Study, as well as Sue Hudson, Helen Wilfehrt, PhD, and Alex Liede, PhD for medical writing assistance which was funded by Amgen Inc.

Notes

*Portions of the data in this manuscript were presented at the American Society of Hematology, December 10–13, 2005, Atlanta, GA, USA