Comparison of darbepoetin alfa dosed weekly (QW) vs. extended dosing schedule (EDS) in the treatment of anemia in patients receiving multicycle chemotherapy in a randomized, phase 2, open-label trial.
BACKGROUND
Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery.


METHODS
This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 μg Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 μg Q3W if chemotherapy was Q3W) or weekly (150 μg QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin (<10 g/dL vs. ≥10 g/dL), and tumor type (lung/gynecological vs. other nonmyeloid malignancies). The primary endpoint was change in hemoglobin from baseline to Week 13.


RESULTS
Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received ≥1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76% in the QW group achieved the target hemoglobin of ≥11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95% confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95% confidence interval was less than the prespecified limit of <0.75 g/dL, supporting noninferiority of the EDS dosing schedule. Reported adverse events were similar between groups. A slight increase in transfusions was reported in the QW group.


CONCLUSIONS
Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules.


BACKGROUND
ClinicalTrials.gov Identifier NCT00144131.
West Clinic, Memphis, TN, USA. lschwartzberg@westclinic.com
Lee
L
Schwartzberg
Ronald
R
Burkes
Barry
B
Mirtsching
Timothy
T
Rearden
Peter
P
Silberstein
Lorrin
L
Yee
Amy
A
Inamoto
Tom
T
Lillie
D000203:Activities of Daily Living; D000368:Aged; D000740:Anemia / Q000139:chemically induced* / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000068256:Darbepoetin alfa; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa