Originally published as JCO Early Release 10.1200/JCO.2007.14.2885 on January 28 2008

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Darbepoetin Alfa for the Treatment of Anemia in Patients With Active Cancer Not Receiving Chemotherapy or Radiotherapy: Results of a Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

Robert E. Smith, Jr, Matti S. Aapro, Heinz Ludwig, Tamás Pintér, Martin makal, Tudor E. Ciuleanu, Li Chen, Tom Lillie, John A. Glaspy

From the South Carolina Oncology Associates, Columbia, SC; Amgen Inc, Thousand Oaks; University of California, Los Angeles, School of Medicine, Los Angeles, CA; Clinique de Genolier, Genolier, Switzerland; Wilhelminenspital, 1.Medizinische Abteilung mit Onkologie, Vienna, Austria; Petz Aladar County Teaching Hospital, Gyor, Hungary; Ustav Onkologie a Pneumologie Na Plesi, Onkologicke oddeleni, Plesi, Czech Republic; and Institutul Oncologic "Ion Chiricuta," Cluj-Napoca, Romania

Corresponding author: John Glaspy, MD, MPH, Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, School of Medicine, 100 UCLA Medical Plaza, Suite 550, Los Angeles, CA 90095-6956; e-mail: jglaspy{at}mednet.ucla.edu

Purpose The efficacy and safety of darbepoetin alfa (DA) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated.

Patients and Methods Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III, multicenter, randomized, placebo-controlled study and administered placebo or DA 6.75 µg/kg every 4 weeks (Q4W) for up to 16 weeks with a 2-year follow-up for survival. Patients who completed 16 weeks of treatment could receive the same treatment as randomized Q4W for an additional 16 weeks. The primary end point was all occurrences of transfusions from weeks 5 through 17; safety end points included incidence of adverse events and survival.

Results The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo. DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period. Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo (P = .022). This effect varied by baseline covariates including, sex, tumor type, and geographic region; statistical significance diminished (P = .12) when the analysis was adjusted for baseline imbalances or known prognostic factors.

Conclusion DA was not associated with a statistically significant reduction in transfusions. Shorter survival was observed in the DA arm; thus, this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer.

Supported by Amgen Inc (Amgen Study ID Nos. 20010103 and 20020149; ClinicalTrials.gov identifiers NCT00091858 [ClinicalTrials.gov] and NCT00115167 [ClinicalTrials.gov] ).

Presented in part at the Annual Meeting of the American Association for Cancer Research, April 14-18, 2007, Los Angeles, CA; and at the 12th Congress of the European Hematology Association, June 7-10, 2007, Vienna, Austria.

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

published online ahead of print at www.jco.org on January 28, 2008.

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