Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV breast cancer

Abstract

Background: In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]).

Objectives: To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective.

Methods: Patient data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles, and adverse events were recorded, with survival follow-up for 12–36 months post-study. Stage IV breast cancer therapy costs were collected by surveying UK oncologists, and utilities for associated health states were from published sources. Costs were in British pounds and year 2000 values. Costs and benefits were jointly determined for the stage IV breast cancer subgroup (n = 55). Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap simulations (10 000 iterations) were conducted to account for uncertainty, and sensitivity analyses were conducted to establish robustness.

Results: The ICUR for epoetin-alfa treatment was £8851 per QALY, with a 99% probability of a positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a 94% probability of being acceptable using a threshold ICUR of £30 000/QALY. The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival.

Conclusions: The available data suggest a high probability of favourable costutility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy. Additional studies are warranted.

Appendix

The following investigators participated in the clinical study: Belgium: Yves Beguin, MD, CHU Sart-Tilman, Liege; Rene Brys, MD, H. Hart Klinick, Ecklo; Gilbert De Wasch, MD, Henri Serruys Hospital, Oostende; Mario Antonio Dicato, MD, Centre Hospitalier de Luxembourg, Luxembourg; Raymond Mathys, MD, A.Z. Middelheim, Antwerpen; M. Symann, MD, Oncologie Médicale, Cliniques St Luc, Brussels; Achiel Van Hoof, MD, Algemeen Ziekenhuis St Jan, Brugge; and Ignace Vergote, MD, U.Z. Gasthuisberg, Leuven. Czech Republic: Otakar Bednarik, MD, Masaryk Memorial Cancer Institute, Brno; Michael Frank, MD, Department of Radiotherapy, Faculty Hospital, Plzen; and Milada Zemanova, MD, Veobecná Fakultni Nemocnice UK, Praha 2. France: Pierre-Etienne Cailleux, MD, Service de Radiotherapie/Chimiotherapie, Tours; Herve Cure, MD, Centre Regional de Lutte, Contre le Cancer Jean Perrin, Clermont-Ferrand; Marine Divine, MD, Hospital Henri Mondor, Creteil; Jean-Paul Guastalla, MD, Centre Regional de Lutte, Contre le Cancer Leon Berard, Lyon; M. Faress Husseini, MD, Hospital Pasteur, Hospitaux Civils Colmar, Colmar; and Hervé Lacroix, MD, CHU-Hospital Laennec, Service D’Oncologie Generale, Nantes. Germany: Gerhard Adam, MD, Asklepios Klinik Triberg, Triberg; Konstantin Akrivakis, MD, Universitätsklinikum Charité, Berlin; Carsten Bokemeyer, MD, Medizinische Universitätsklinik Abt. II, Eberhard-Karls Universität, Tübingen; Lothar Böning, MD, Onkologische Praxisgemeinschaft, München; Mathias Freund, MD, Abteilung Hämatologic/Onkologic, Klinik und Poliklinik für Innere Medizin, Rostock; Hans-Jürgen Hurtz, MD, Onkologische Gemeinschaftspraxis, Halle; Hartmut Kirchner, MD, Siloa Hospital, Clinic for Hematology and Oncology, Hannover; Erhard Kurschel, MD, Gemeinschaftspraxis, Oberhausen; Wolf- Dieter Ludwig, MD, Virchow-Klinikum, Robert-Rössle-Klinik, Berlin; Norbert Marschner, MD, Praxis in der Klinik für Tumorbiologie, Freiburg; Karl Ulrich Petry, MD, Frauenklinik der MHH, Hannover; Uwe Reinhardt, MD, Klinikum Bayreuth, Abteilung Onkologie, Bayreuth; Peter Reitzig, MD, Humaine Klinik, Dresden; and Wolfgang Schuette, MD, City Hospital Martha-Maria, Hämatologie, Halle. Greece: Vassilis Georgoulias, MD, University Hospital of Heraklion, Department of Clinical Oncology, Heraklion, Crete; Gerasimos Pangalis, MD, Laikon General Hospital, Athens; Nicholas Pavlidis, MD, University Hospital of Ioannina, Ioannina; and Dimostenis-Vasilios Skarlos, MD, Agii Anargiri Cancer Hospital, Athens. Hungary: Tamás Pintér, MD, Petz Aladár County Hospital, Gyõr, Department Oncoradiology, Gyõr; Gyula Szegedi, MD, Debrecen University Medical School, Third Department for Internal Medicine, Debrecen; and Gyula Varga, MD, Albert Szent-Gyocrgyi Med. University Szeged, Second Department of Internal Medicine, Szeged. Ireland: John Rory O’Donnell, MD, Beaumont Hospital, Dublin. Italy: Emilio Bajetta, MD, Instituto Nazionale Per Lo Studio E La Cura dei Tumori, Milan; Agostino Cortelezzi, MD, Università Degli Studi di Milano, Ospedale Policlinico, Cattedra Di Ematologia, Milan; and Gabriella Gorzegno, MD, Osperdale S. Luigi, Istituto di Clinica Medica Generale, Orbassano (Torino). The Netherlands: Franciscus L.G. Erdkamp, MD, Maaslandziekenhuis, Sittard; H.J. Keizer, MD, Academisch Ziekenhuis Leiden, Leiden; J.J. Mol, MD, Ziekenenhuis Rijnstate, Arnhem; Johan W.R. Nortier, MD, Diakonessenhuis, Utrecht; Ron C. Rietbrock, MD, Academisch Medisch Centrum, Amsterdam; C.J. Rodenburg, MD, Algemeen Christelijk Ziekenhuis Eemland, Lokatie De Lichtenberg, Amersfoort; M.R. Schaafsma, MD, Medisch Spectrum Twente, Enschede; L.H. Siegenbeek van Heukclom, MD, Medisch Centrum Alkmaar, Alkmaar; C. van der Heul, MD, Sint Elisabeth Ziekenhuis, Tilburg; Marinus Van Marwijk Kooy, MD, St Sophia Ziekenhuis, Zwolle; Gerard Vreugdenhil, MD, Sint Joseph Ziekenhuis, Veldhoven; and Jacques Wils, MD, Laurentius Hospital, Roermond. Poland: Jerzy Holowiecki, MD, Department of Haematology, Silesian School of Medicine, Katowice; Marek Pawlicki, MD, Maria Skiodowska-Curie Memorial Cancer Center, Division in Cracow, Kraków; and Piotr Siedlecki, MD, Maria Skiodowska-Curie Memorial Cancer Center, Warsaw, Warszawa. Portugal: Cândida Azevedo, MD, Instituto Português de Oncologia, Porto; Ricardo Marques da Costa, MD, Hospital Dristrital de Leiria, Leiria; and Joaquim Gouveia, MD, Hospital de Santo António dos Capuchos, Lisboa. South Africa: Dayle Hacking, MD, Durban Oncology Center, Westridge, Durban; Johann Raats, MD, 110 Dmar Medical Center, Capetown; and Bernardo Rapoport, MD, The Medical Oncology Center of Rosebank, Johannesburg. Switzerland: Matti S. Aapro, MD, Centre Anticancéreux, Genolier; Richard Herrmann, MD, Kantonspital Basel, Basel; J.M. Lüthi, MD, Regionalspital Thun, Thun; and Kaspar Rhyner, MD, Kantonspital Glarus, Glarus. United Kingdom: Peter Jeffrey Barrett-Lee, MD, Department of Oncology, Velindre Hospital, Cardiff; David Fairlamb, MD, New Cross Hospital, Ceansly Center, Wolverhampton; Riaz Jan-Mohamed, MD, Hillingdon Hospital, Uxbridge; Timothy James Littlewood, MD, John Radcliffe Hospital, Oxford; Graham Smith, MD, Royal United Hospital, Bath; and John Sweetenham, MD, Southampton General Hospital, CRC Oncology Unit, Southampton.