Therapeutic effects of epoetin zeta in the treatment of chemotherapy-induced anaemia

ABSTRACT

Objective: To perform an open, non-controlled, multiple-dose, international, multicentre, phase III study to evaluate epoetin zeta, a biosimilar epoetin referenced to epoetin alfa, for the treatment of chemotherapy-induced anaemia in patients with cancer.

Methods: Safety, tolerability and efficacy of subcutaneously administered epoetin zeta were assessed in 216 patients with solid tumours or non-myeloid haematological malignancies receiving chemotherapy and at risk of transfusion.

Results: A significant (p < 0.0001) increase in mean haemoglobin (Hb) level (1.8 g/dL) was observed between baseline and week 12 (intent-to-treat population); 176/216 (81.5%) patients achieved a response (increase in Hb ≥ 1 g/dL or reticulocyte count ≥40 000 cells/μL) by week 8. Over the treatment period, 231 treatment-emergent adverse events were experienced by 91 patients; 9/216 (4.2%) experienced a clinically significant thrombotic event within the first 12 weeks of epoetin zeta treatment, significantly lower than the assumed 18% baseline incidence (p < 0.0001) based on historical data from epoetin trials. No transfusion was necessary for 175/216 patients (81.0%) and quality of life improved over the study. No patients developed anti-erythropoietin antibodies. Sponsor trial no: CT-830-05-0009.

Conclusion: This study demonstrates that subcutaneously administered epoetin zeta is well-tolerated and has efficacy in the treatment of anaemia in patients with cancer receiving chemotherapy and at risk of transfusion.

Keywords: :

• Anaemia
• Chemotherapy
• Epoetin zeta
• Erythropoietin
• Safety

Transparency

Declaration of funding

This study was sponsored by STADA R&D GmbH, Bad Vilbel, Germany (Epoetin CT-830-05-0009 study [sponsor study number]/411-54-04-46-0000 [CRO study code]). Hospira (which distributes epoetin zeta [Retacrit] in Europe) funded the medical writing/editorial assistance and the publication support of the article, including the work of CCDRD AG. The authors take full responsibility for the content of the article.

Declaration of financial/other relationships

R.K. has disclosed that he is an employee of CCDRD AG and has received honoraria from Hospira for presentations at meetings. V.T. and G.M have disclosed that they have no relevant financial relationship. I.E. has disclosed no relevant financial relationships.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed they have no relevant financial relationships.

Acknowledgments

The authors thank Jenny Fanstone of Caudex Medical Ltd (supported by Hospira) for her assistance in preparing the initial draft of the manuscript and collating the comments of authors and other named contributors, as well as Dr Michael Wolf-Pflugmann, Dr Marianne Siebert-Weigel, Dr Peter Hansen, and Jan-Ole Hesse for their valued contribution to this study.

Parts of the data discussed here were presented at the 33rd European Society for Medical Oncology Congress; Stockholm, Sweden, 12–16 September 2008 (Poster 907P; Poster 906P).

The authors also would like to thank the following fellow Epoetin Zeta Oncology Study Group Investigators: Bulgaria: Assoc. Prof. J. Raynov, Assoc. Prof. D. Hodjadjik, Assoc. Prof. L. Gercheva, Assoc. Prof. A. Deleva, Prof. G. Gorchev, Assoc. Prof. N. Tsvetkov, P. Lishkovska, Assoc. Prof. H. Ganchev, T. Koynova; Poland: E. Wójcik, A. Roszak, P. Sawrycki, M. Zemła, Prof. I. Rzepka-Górska, R. Surma-Włodarczyk, A. Rozmiarek, B. Utracka-Hutka; Serbia: S. Jelic, A. Dagovic, Doc. N. Andjelkovic, Prof. S. Radic, M. Vucic, Doc. S. Ristic

Notes

* Retacrit is a registered trade name of Hospira Enterprises B.V., Hoofddorp, the Netherlands

† Silapo is a registered trade name of STADA Arzneimittel AG, Bad Vilbel, Germany