Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) approved in the USA for treating chemotherapy-induced anemia. However, cancer patients (pts) not receiving chemotherapy can still develop anemia of cancer (AoC), which is often not treated (

Ludwig et al. Eur J Cancer. 2004;40:2293–2306
). As pts with AoC are not receiving chemotherapy or radiotherapy and may have few clinic visits, using an ESA with a long dosing interval, such as once monthly (Q4W), may be optimal for these pts. Results from a prior study suggested that Q4W dosing of DA is feasible since 61% of pts (n=21) with AoC receiving 6.75mcg/kg DA Q4W achieved a hematopoietic response (≥2g/dL hemoglobin [Hb] rise from baseline or Hb ≥12g/dL without a red blood cell transfusion in the prior 28 days) (
Smith et al. Br J Cancer. 2003;88:1851–1858
). Here we report the final results of a phase 2, randomized, double-blind, placebo-controlled study of DA Q4W in pts with AoC. Pt eligibility included ≥18 years, non-myeloid malignancy, AoC (Hb ≤11g/dL), and no chemotherapy and/or radiotherapy within 30 days of screening or during the study. Pts (n=220) were randomized 3:1 to DA (6.75mcg/kg) or placebo (PBO), with stratification based on screening Hb (<10g/dL or ≥10g/dL). Pts received blinded treatment (DA or PBO) subcutaneously Q4W for 13 weeks (4 total doses); end of study was week 17. The primary endpoint was the percentage of pts with a hematopoietic response. Of the 162 DA pts, 63% were female, 73% were white, and the mean (SD) age was 70 (12) years; the 56 PBO pts had similar demographics. The Kaplan-Meier percentage (KM%) of pts with a hematopoietic response (Table) differed significantly between the DA and PBO groups (% difference [95% CL]=44% [30, 58]; p<0.001). The two groups also differed significantly in the KM% of pts who achieved the target Hb of 11g/dL (% difference [95% CL]=38% [22, 54]; p<0.001). Adverse events (AEs) occurred in 71% DA pts (116/164) and 72% PBO pts (39/54); the most common AE was fatigue. The incidence was 3% vs 2% for treatment-related AEs and 28% vs 28% for serious AEs in the DA and PBO groups, respectively. In 30% DA pts and 4% PBO pts, Hb reached >13g/dL. Serious thromboembolic events (deep vein thrombosis, cerebrovascular accident, and pulmonary embolism) occurred in 2.4% DA pts and in 0% PBO pts. In summary, DA Q4W appeared to be effective and well tolerated in this study for the treatment of AoC.

Summary of Hb Results

DAPBO
n=162n=56
*LVCF=Last value carried forward 
Hematopoietic Response  
Pts eligible for hematopoietic response analysis, n 158 54 
KM% (95% CL) pts with hematopoietic response 69% (61, 77) 24% (12, 36) 
Target Hb  
Pts eligible for target Hb analysis, n 139 49 
KM% (95% CL) pts achieved target Hb (11g/dL) 85% (79, 92) 50% (34, 66) 
Mean (SD) Hb after target achieved, g/dL 11.9 (0.8) [n=133] 11.3 (0.8) [n=28] 
Change in Hb from Baseline to Week 17 (LVCF*)  
Pts eligible for analysis of change in Hb, n 158 54 
Mean (SD) baseline Hb, g/dL 10.1 (0.8) 10.2 (0.8) 
Mean (SD) Hb change (baseline to week 17), g/dL 1.3 (1.4) 0.2 (1.0) 
DAPBO
n=162n=56
*LVCF=Last value carried forward 
Hematopoietic Response  
Pts eligible for hematopoietic response analysis, n 158 54 
KM% (95% CL) pts with hematopoietic response 69% (61, 77) 24% (12, 36) 
Target Hb  
Pts eligible for target Hb analysis, n 139 49 
KM% (95% CL) pts achieved target Hb (11g/dL) 85% (79, 92) 50% (34, 66) 
Mean (SD) Hb after target achieved, g/dL 11.9 (0.8) [n=133] 11.3 (0.8) [n=28] 
Change in Hb from Baseline to Week 17 (LVCF*)  
Pts eligible for analysis of change in Hb, n 158 54 
Mean (SD) baseline Hb, g/dL 10.1 (0.8) 10.2 (0.8) 
Mean (SD) Hb change (baseline to week 17), g/dL 1.3 (1.4) 0.2 (1.0) 
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Topics:
cancer, cancer anemia, chemotherapy regimen, darbepoetin alfa, radiation therapy, brachial plexus neuritis, screening, adverse event, anemia, cerebrovascular accident

Disclosures: Darbepoetin alfa is not FDA-approved for the treament of anemia of cancer. In addition, data on Q4W dosing of darbepoetin alfa and on unlicensed doses of darbepoetin alfa are included in the abstract. The efficacy of darbepoetin alfa for correcting anemia in patients with chemotherapy-induced anemia has generated interest in the efficacy of this erythropoiesis-stimulating protein for treating anemia of cancer.; Dr. Lam: Employee of Amgen Inc.; Dr. Lillie: Full time employee of Amgen Inc (manufacturer of darbepoetin alfa).; Dr. Gordon: executed service letter agreement with Amgen; Dr. Miller: consultant to Amgen.; Dr. Gordon: ownership of Amgen stock; Dr. Lam: ownership of Amgen stock options; Dr. Lillie: ownership of stock and stock options in Amgen Inc.; Dr. Miller: ownership of Amgen stock during the last 2 years.; Amgen funded this anemia of cancer study in which Dr. Gordon, Dr. Nichols, Dr. Ben-Jacob, and Dr. Miller were investigators.; Dr. Gordon: Honorarium from Amgen for presentation and participation in national investigator’s meeting; Dr. Miller: honoraria from Amgen.; Dr. Miller: On the Amgen Speakers Bureau.

Author notes

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Corresponding author

2006, The American Society of Hematology
2006
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