Originally published as JCO Early Release 10.1200/JCO.2008.19.1130 on April 20 2009

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Pooled Analysis of Individual Patient-Level Data From All Randomized, Double-Blind, Placebo-Controlled Trials of Darbepoetin Alfa in the Treatment of Patients With Chemotherapy-Induced Anemia

From the Wilhelminenspital, Department of Medicine I, Center for Oncology and Hematology, Vienna, Austria; Duke University Medical Center, Durham, NC; Departments of Hematology and Oncology, Karolinska University Hospital, Stockholm, Sweden; Respiratory Oncology Unit, Department of Pulmonology, University Hospital Gasthuisberg, Leuven, Belgium; Pennsylvania Oncology Hematology Associates, Philadelphia, PA; Amgen Inc, Thousand Oaks; and University of California, Los Angeles, School of Medicine, Los Angeles, CA.

Corresponding author: Heinz Ludwig, MD, Department of Medicine I, Center for Oncology and Hematology, Pavillion 23, Montleartstrasse 37, 1160 Vienna, Austria; e-mail: heinz.ludwig{at}wienkav.at.

Purpose Although numerous clinical trials have demonstrated the efficacy and tolerability of erythropoiesis-stimulating agents (ESAs) in patients with chemotherapy-induced anemia (CIA), results of some recent trials and one meta-analysis have suggested that ESAs may negatively impact survival and/or disease control in patients with cancer.

Methods To assess the benefits and risks of ESAs in CIA, we conducted a pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials in 2,122 patients with CIA receiving darbepoetin alfa (DA; n = 1,200) or placebo (n = 912).

Results DA did not increase mortality (hazard ratio = 0.97; 95% CI, 0.85 to 1.1) and had no effect on progression-free survival (hazard ratio = 0.93; 95% CI, 0.84 to 1.04) and disease progression (hazard ratio = 0.92; 95% CI, 0.82 to 1.03), but, as expected, increased the risk for thromboembolic events (hazard ratio = 1.57; 95% CI, 1.10 to 2.26). Overall and progression-free survival were not affected by baseline hemoglobin and seemed better in patients who achieved hemoglobin more than 12 or more than 13 g/dL. Transfusions and rates of hemoglobin increase (> 1 g/dL in 14 days; > 2 g/dL in 28 days) owing to transfusions were associated with an increased risk for death and disease progression in both treatment groups; in the absence of transfusions, rates of hemoglobin increase did not appear to increase the risk for adverse outcomes. Compared with placebo, DA significantly reduced the risk of receiving one or more transfusion.

Conclusion There seemed to be no association between DA and risk of death or disease progression in this meta-analysis of individual patient data from DA studies conducted in CIA, the approved indication for ESAs in oncology.

Supported (analysis) by Amgen Inc.

Presented in part at the 14th European Cancer Conference, September 23-27, 2007, Barcelona, Spain; the American Society of Hematology 49th Annual Meeting and Exposition, December 8-11, 2007, Atlanta, GA; and the Hematology Oncology Pharmacy Association/International Society of Oncology Pharmacy Practitioners Joint Annual Conference, June 18-21, 2008, Anaheim, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: AMG 980291, AMG 20010145, AMG 990114, AMG 20030232, AMG 98297.

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