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Transfusion risk in cancer patients with chemotherapy-induced anemia when initiating darbepoetin alfa therapy at a baseline hemoglobin level of <9 g/dL versus 9 to <10 g/dL versus ≥10 g/dL: an exploratory analysis of a phase 3 trial

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Abstract

Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia (CIA). Safety concerns have prompted changes to the ESA-product information, which now recommends initiating ESAs at hemoglobin (Hb) levels <10 g/dL (US) or ≤10 g/dL (EU). The present exploratory analysis of a DA trial examined how baseline-Hb levels at ESA initiation affect transfusion rates, Hb response, and safety outcomes in CIA patients. Data were retrospectively analyzed from a phase 3 trial of CIA patients randomised to 500 mcg DA every 3 weeks (Q3 W) or to 2.25 mcg/kg DA weekly (QW) for 15 weeks. In the current analysis, data were reanalyzed by baseline-Hb categories of <9 g/dL (n = 126), 9 to <10 g/dL (n = 225), and ≥10 g/dL (n = 354). The Q3 W and QW groups were combined. Transfusion rates were highest in the <9 g/dL baseline-Hb group in all time periods examined. The Kaplan–Meier percentage (95% CI) of patients achieving Hb ≥10 g/dL was 68% (59, 78) and 88% (82, 92) in the <9 g/dL and 9 to <10 g/dL baseline-Hb groups, respectively. With lower baseline-Hb, incidence of a ≥1 g/dL-Hb rise in 14 days progressively decreased. Incidence of venous thromboembolic events was similar in all baseline-Hb groups and similar between patients with or without a ≥1 g/dL-Hb rise in 14 days. Overall, transfusion risk increased and Hb response decreased at lower baseline-Hb levels in this exploratory analysis. When following ESA-product information to initiate ESAs at Hb ≤ 10 g/dL, the greatest benefit may be achieved when initiating close to 10 g/dL. Prospective studies are needed to further examine this hypothesis.

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Acknowledgments

This study was sponsored by Amgen Inc. The authors wish to thank Linda Rice, PhD, at Amgen Inc. for assistance with the writing of this manuscript and Matt Ness at Amgen Inc. for programming support.

Conflict of interest

J-L. Canon has had a consultant/advisory role with Amgen Inc. and has received funding from Amgen Inc. J. Vansteenkiste is holder of the Amgen Chair for Supportive Cancer Care at Leuven University (i.e., has received research funding from Amgen Inc.). M. Hedenus has received minor remuneration from Amgen Inc. P. Gascon declares no conflict of interest. C. Bokemeyer has had a consultant/advisory role with Amgen Inc. and Hexal AG. H. Ludwig has had a consultant/advisory role with Amgen Inc., Centocor Ortho Biotech Inc., Hoffman-La Roche Ltd, and Sandoz International GmbH; he has also received research funding from Amgen Inc. J. Vermorken has received remuneration from Amgen Inc. and has had a consultant/advisory role with Amgen Inc. J. Legg has received remuneration from Amgen Inc. as an Amgen employee and owns Amgen Inc. stock. B. Pujol has received remuneration from Amgen Inc. as an Amgen employee and owns Amgen Inc. stock. K. Bridges has received funding from Amgen Inc. as a former Amgen employee and owns Amgen Inc. stock.

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Author notes

  1. Ken Bridges

    Present address: Onyx Pharmaceuticals Inc., South San Francisco, CA, 94080, USA

Authors and Affiliations

  1. Oncology-Hematology Department, Grand Hopital de Charleroi, 3 Grand Rue, 6000, Charleroi, Belgium

    Jean-Luc Canon

  2. Respiratory Oncology Unit (Pulmonology), University Hospital Gasthuisberg, 3000, Leuven, Belgium

    Johan Vansteenkiste

  3. Department of Internal Medicine, Sundsvall Hospital, 851 86, Sundsvall, Sweden

    Michael Hedenus

  4. Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain

    Pere Gascon

  5. Department of Oncology, Hematology with Section Pneumology, University Hospital Hamburg Eppendorf, 20246, Hamburg, Germany

    Carsten Bokemeyer

  6. First Department of Medicine, Center for Oncology and Haematology, Wilhelminenspital der Stadt Wien, 1171, Vienna, Austria

    Heinz Ludwig

  7. Department of Medical Oncology, Antwerp University Hospital, 2650, Edegem, Belgium

    Jan Vermorken

  8. Department of Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, 91320, USA

    Jason Legg

  9. Department of International Oncology, Amgen Europe, 6300, Zug, Switzerland

    Beatriz Pujol

  10. Department of Hematology/Oncology, Amgen Inc., Thousand Oaks, CA, 91320, USA

    Ken Bridges

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  1. Jean-Luc Canon
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Correspondence to Jean-Luc Canon.

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Canon, JL., Vansteenkiste, J., Hedenus, M. et al. Transfusion risk in cancer patients with chemotherapy-induced anemia when initiating darbepoetin alfa therapy at a baseline hemoglobin level of <9 g/dL versus 9 to <10 g/dL versus ≥10 g/dL: an exploratory analysis of a phase 3 trial. Med Oncol 29, 2291–2299 (2012). https://doi.org/10.1007/s12032-011-0103-x

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  • DOI: https://doi.org/10.1007/s12032-011-0103-x

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