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The economic value of primary prophylaxis using pegfilgrastim compared with filgrastim in patients with breast cancer in the UK

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Abstract

Background

Febrile neutropenia (FN) is a serious adverse event associated with myelotoxic chemotherapy that predisposes patients to life-threatening bacterial infections. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) from the first cycle of chemotherapy is recommended by the 2006 American Society of Clinical Oncology, 2008 National Comprehensive Cancer Network and 2006 European Organisation for Research and Treatment of Cancer guidelines when the overall risk of FN is approximately 20% or higher. Once-per-cycle pegfilgrastim and daily filgrastim are two commonly used G-CSFs with different dosing schedules and associated costs.

Objective

To evaluate the cost effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the UK.

Methods

A decision-analytic model was constructed from the UK NHS perspective with a lifetime study horizon. The model simulated three clinical scenarios: scenario 1 assumed that pegfilgrastim and filgrastim had differential impact on the risk of FN; scenario 2 assumed additional differential impact on FN-related mortality; and scenario 3 assumed additional differential impact on chemotherapy relative dose intensity (RDI) with long-term survival effects. The base-case population included 45-year-old women with stage II breast cancer receiving four chemotherapy cycles, with an FN risk of approximately 20% or higher.

Model inputs, including FN risk, FN case-fatality, RDI, impact of RDI on survival and utility scores, were based on a review of the literature and expert panel validation. Using data from the literature, it was estimated that the absolute risk of FN associated with pegfilgrastim was 5.5% lower than with 11-day filgrastim (7% vs 12.5%), and 10.5% lower than with 6-day filgrastim (7% vs 17.5%). Costs were taken from official price lists or the literature and included drugs, drug administration, FN-related hospitalizations and subsequent medical costs. Breast cancer mortality and all-cause mortality were obtained from official statistics. The main outcome measures were the costs (d, year 2006 values) per percentage decrease in (absolute) FN risk, per FN event avoided, per life-year gained (LYG), and per QALY gained. Model robustness was tested using deterministic and probabilistic sensitivity analyses.

Results

Pegfilgrastim was cost saving compared with 11-day filgrastim (£3196 vs £4315). Compared with 6-day filgrastim, pegfilgrastim was associated with a cost of £4200 per FN event avoided, or £42 per 1% decrease in absolute risk of FN, in scenario 1. In scenario 2, pegfilgrastim provided 0.055 more LYGs or 0.052 more QALYs at a minimal cost increase of d441 (£3196 vs £2754) per person, yielding an incremental cost-effectiveness ratio (ICER) of £8075/LYG or £8526/QALY. In scenario 3, when all potential benefits of G-CSF were considered, the ICER became £3955/LYG or £4161/QALY. Results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim.

Conclusions

In this UK analysis, pegfilgrastim appears to dominate 11-day use of filgrastim. The value of pegfilgrastim versus 6-day filgrastim at £4161-8526/QALY was very favourable compared with the commonly used threshold in the UK. In this setting, primary prophylaxis with pegfilgrastim may be cost effective compared with filgrastim.

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References

  1. Smith T, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24(19): 3187–205

    Article  PubMed  CAS  Google Scholar 

  2. Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 1991; 325(3): 164–70

    Article  PubMed  CAS  Google Scholar 

  3. Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 29A(3): 319–24

    Article  PubMed  CAS  Google Scholar 

  4. Holmes FA, O’shaughnessy JA, Vukelja S, et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 2002; 20(3): 727–31

    Article  PubMed  CAS  Google Scholar 

  5. Green MD, Koelbl H, Baselga J, et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003; 14(1): 29–35

    Article  PubMed  CAS  Google Scholar 

  6. Vogel CL, Wojtukiewicz MZ, Carroll RR, et al. First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol 2005; 23(6): 1178–84

    Article  PubMed  CAS  Google Scholar 

  7. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: myeloid growth factors, version 1.2008 [online]. Available from URL: http://www.nccn.org/professionals/physician_gls/PDF/myeloid_growth.pdf [Accessed 2008 Jun 26]

  8. Aapro MS, Cameron DA, Pettengell R, et al. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer 2006; 42(15): 2433–53

    Article  PubMed  CAS  Google Scholar 

  9. Glaspy JA, Bleecker G, Crawford J, et al. The impact of therapy with filgrastim (recombinant granulocyte colony-stimulating factor) on the health care costs associated with cancer chemotherapy. Eur J Cancer 1993; 29ASuppl. 7: S23–30

    Article  PubMed  Google Scholar 

  10. Pinto L, Liu Z, Doan Q, et al. Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: a meta-analysis of randomized controlled trials. Curr Med Res Opin 2007; 23(9): 2283–95

    Article  PubMed  CAS  Google Scholar 

  11. Siena S, Piccart MJ, Holmes FA, et al. A combined analysis of two pivotal randomized trials of a single dose of pegfilgrastim per chemotherapy cycle and daily filgrastim in patients with stage II-IV breast cancer. Oncol Rep 2003; 10(3): 715–24

    PubMed  CAS  Google Scholar 

  12. von Minckwitz G, Kummel S, du Bois A, et al. Pegfilgrastim +/− ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer: results from the GEPARTRIO study. Ann Oncol 2008; 19(2): 292–8

    Article  Google Scholar 

  13. Weycker D, Hackett J, Edelsberg JS, et al. Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization? Ann Pharmacother 2006; 40(3): 402–7

    Article  PubMed  CAS  Google Scholar 

  14. Scott SD, Chrischilles EA, Link BK, et al. Days of prophylactic filgrastim use to reduce febrile neutropenia in patients with non-Hodgkin’s lymphoma treated with chemotherapy. J Manag Care Pharm 2003; 9(2 Suppl.): 15–21

    PubMed  Google Scholar 

  15. Green MD, Lu ZJ. Once-per-cycle fixed-dose administration of pegfilgrastim reduced resource utilization and cost compared with daily filgrastim in the prevention of chemotherapy-induced neutropenia [abstract and poster]. International Society for Pharmacoeconomics and Outcomes Research, 5th Annual European Congress; 2002 Nov 3–5; Rotterdam

  16. Heckinger EA, Lee J, Calhoun E, et al. Cost minimization analysis of filgrastim (G-CSF) versus pegfilgrastim (peg-GCSF) for stage II-IV breast cancer patients receiving chemotherapy: assessments based on third-party and societal perspectives [abstract no. 2116]. Presented at the American Society of Clinical Oncology 39th Annual Meeting; 2003 May 31-Jun 3; Chicago (IL)

  17. Adams JR, Angelotta C, Bennett CL. Prophylactic colony-stimulating factor use when the risk of febrile neutropenia is 20%: it is clinically effective, but is it cost-effective? J Clin Oncol 2006; 24(19): 2975–9

    Article  PubMed  Google Scholar 

  18. Hershman D, McBride R, Jacobson JS, et al. Racial disparities in treatment and survival among women with early-stage breast cancer. J Clin Oncol 2005; 23(27): 6639–46

    Article  PubMed  Google Scholar 

  19. Morrow T, Siegel M, Boone S, et al. Chemotherapy dose intensity determination as a quality of care measure for managed care organizations in the treatment of early-stage breast cancer. Am J Med Qual 2002; 17(6): 218–24

    Article  PubMed  Google Scholar 

  20. Colleoni M, Li S, Gelber RD, et al. Relation between chemotherapy dose, oestrogen receptor expression, and body-mass index. Lancet 2005; 366(9491): 1108–10

    Article  PubMed  CAS  Google Scholar 

  21. Bonadonna G, Moliterni A, Zambetti M, et al. 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ 2005; 330(7485): 217. Epub 2005 Jan 13

    Article  PubMed  Google Scholar 

  22. Bonadonna G, Valagussa P, Moliterni A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 1995; 332(14): 901–6

    Article  PubMed  CAS  Google Scholar 

  23. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 1981; 304(1): 10–5

    Article  PubMed  CAS  Google Scholar 

  24. Lyman GH, Dale DC, Friedberg J, et al. Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol 2004; 22(21): 4302–11

    Article  PubMed  CAS  Google Scholar 

  25. Curtis L, Netten A. Unit costs of health and social care. Canterbury: Personal Social Services Research Unit, 2005

    Google Scholar 

  26. Hackshaw A, Sweetenham J, Knight A. Are prophylactic haematopoietic growth factors of value in the management of patients with aggressive non-Hodgkin’s lymphoma? Br J Cancer 2004; 90(7): 1302–5

    Article  PubMed  CAS  Google Scholar 

  27. Timmer-Bonte JN, Adang EM, Smit HJ, et al. Cost-effectiveness of adding granulocyte colony-stimulating factor to primary prophylaxis with antibiotics in patients with small-cell lung cancer. J Clin Oncol 2006; 24(19): 2991–7

    Article  PubMed  CAS  Google Scholar 

  28. Lyman GH, Kuderer NM. The economics of the colony-stimulating factors in the prevention and treatment of febrile neutropenia. Crit Rev Oncol Hematol 2004; 50(2): 129–46

    Article  PubMed  CAS  Google Scholar 

  29. Caggiano V, Weiss RV, Rickert TS, et al. Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 2005; 103(9): 1916–24

    Article  PubMed  Google Scholar 

  30. Kuderer NM, Dale DC, Crawford J, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 2006; 106(10): 2258–66

    Article  PubMed  Google Scholar 

  31. Leonard RC, Miles D, Thomas R, et al. Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of primary breast cancer patients. Br J Cancer 2003; 89(11): 2062–8

    Article  PubMed  CAS  Google Scholar 

  32. Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005; 352(22): 2302–13

    Article  PubMed  CAS  Google Scholar 

  33. Hillner BE, Smith TJ, Desch CE. Efficacy and cost-effectiveness of autologous bone marrow transplantation in metastatic breast cancer: estimates using decision analysis while awaiting clinical trial results. JAMA 1992; 267(15): 2055–61

    Article  PubMed  CAS  Google Scholar 

  34. Brown RE, Hutton J, Burrell A. Cost effectiveness of treatment options in advanced breast cancer in the UK. Pharmacoeconomics 2001; 19(11): 1091–102

    Article  PubMed  CAS  Google Scholar 

  35. Brown RE, Hutton J. Cost-utility model comparing docetaxel and paclitaxel in advanced breast cancer patients. Anticancer Drugs 1998; 9(10): 899–907

    Article  PubMed  CAS  Google Scholar 

  36. Armstrong K, Chen TM, Albert D, et al. Cost-effectiveness of raloxifene and hormone replacement therapy in postmenopausal women: impact of breast cancer risk. Obstet Gynecol 2001; 98(6): 996–1003

    Article  PubMed  CAS  Google Scholar 

  37. Liljegren G, Karlsson G, Bergh J, et al. The cost-effectiveness of routine postoperative radiotherapy after sector resection and axillary dissection for breast cancer stage I: results from a randomized trial. Ann Oncol 1997; 8(8): 757–63

    Article  PubMed  CAS  Google Scholar 

  38. Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist 2005; 10(6): 427–37

    Article  PubMed  Google Scholar 

  39. Shayne M, Crawford J, Dale DC, et al. Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy. Breast Cancer Res Treat 2006; 100(3): 255–62

    Article  PubMed  Google Scholar 

  40. Lyman GH, Crawford J, Dale D, et al. Clinical prediction models for febrile neutropenia (FN) and relative dose intensity (RDI) in patients receiving adjuvant breast cancer chemotherapy. Proc Am Soc Clin Oncol 2001; 20: 394A

    Google Scholar 

  41. Lyman GH, Dale DC, Crawford J. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J Clin Oncol 2003; 21(24): 4524–31

    Article  PubMed  Google Scholar 

  42. Cancer Research UK. CancerStats factsheet, breast cancer [online]. Available from URL: http://publications.cancerresearchuk.org/WebRoot/crukstoredb/CRUK_PDFs/CSFSBREAST.pdf [Accessed 2008 Mar 17]

  43. Office for National Statistics UK. Long-term breast cancer survival, England and Wales, up to 2003 [online]. Available from URL: http://www.statistics.gov.uk/statbase/ssdataset.asp?vlnk=9132&More=Y [Accessed 2008 Mar 17]

  44. Office for National Statistics UK. Mortality statistics: review of the Register General on deaths by cause, sex and age, in England and Wales, 2004. Series DH2 no. 31 [online] Available from URL: http://www.statistics.gov.uk/statbase/Product.asp?vlnk=618 [Accessed 2009 Aug 10]

  45. Cosler LE, Sivasubramaniam V, Agboola O, et al. Effect of outpatient treatment of febrile neutropenia on the risk threshold for the use of CSF in patients with cancer treated with chemotherapy. Value Health 2005; 8(1): 47–52

    Article  PubMed  Google Scholar 

  46. Talcott JA, Siegel RD, Finberg R, et al. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol 1992; 10(2): 316–22

    PubMed  CAS  Google Scholar 

  47. Klastersky J, Paesmans M, Georgala A, et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin Oncol 2006; 24(25): 4129–34

    Article  PubMed  CAS  Google Scholar 

  48. Chamilos G, Bamias A, Efstathiou E, et al. Outpatient treatment of low-risk neutropenic fever in cancer patients using oral moxifloxacin. Cancer 2005; 103(12): 2629–35

    Article  PubMed  CAS  Google Scholar 

  49. Uys A, Rapoport BL, Anderson R. Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score. Support Care Cancer 2004; 12(8): 555–60

    Article  PubMed  Google Scholar 

  50. Girmenia C, Russo E, Carmosino I, et al. Early hospital discharge with oral antimicrobial therapy in patients with hematologic malignancies and low-risk febrile neutropenia. Ann Hematol 2007; 86(4): 263–70

    Article  PubMed  Google Scholar 

  51. Weinstein MC, Siegel JE, Gold MR, et al. Recommendations of the panel on cost-effectiveness in health and medicine. JAMA 1996; 276(15): 1253–8

    Article  PubMed  CAS  Google Scholar 

  52. Evans C, Tavakoli M, Crawford B. Use of quality adjusted life years and life years gained as benchmarks in economic evaluations: a critical appraisal. Health Care Manag Sci 2004; 7(1): 43–9

    Article  PubMed  Google Scholar 

  53. Center on the Evaluation of Value and Risk in Health. The Cost-Effectiveness Analysis Registry [online]. Available from URL: http://www.tufts-nemc.org/cearegistry/ [Accessed 2007 Feb 23]

  54. Szucs TD, Standaert B, Lu JZ. Analysis of cost difference between daily Neupogen® and once per cycle Neulasta® for prophylaxis against chemotherapy-induced neutropenia France and Germany [abstract and poster]. International Society for Pharmacoeconomics and Outcomes Research, 6th Annual European Congress; 2003 Nov 9–11; Barcelona

  55. Lyman G, Lalla A, Barron R, et al. Cost-effectiveness of pegfilgrastim versus 6-day filgrastim versus 6-day filgrastim primary prophylaxis in patients with non-Hodgkin’s lymphoma receiving CHOP-21 in United States. Curr Med Res Opin 2009; 25(2): 401–41

    Article  PubMed  CAS  Google Scholar 

  56. Cosler LE, Calhoun EA, Agboola O, et al. Effects of indirect and additional direct costs on the risk threshold for prophylaxis with colony-stimulating factors in patients at risk for severe neutropenia from cancer chemotherapy. Pharmacotherapy 2004; 24(4): 488–94

    Article  PubMed  Google Scholar 

  57. Earle CC, Chapman RH, Baker CS, et al. Systematic overview of cost-utility assessments in oncology. J Clin Oncol 2000; 18(18): 3302–17

    PubMed  CAS  Google Scholar 

  58. Neulasta® summary of product characteristics: EU [package insert]. Breda: Amgen Europe, 2009 Apr 17

  59. Friedberg M, Saffran B, Stinson TJ, et al. Evaluation of conflict of interest in economic analyses of new drugs used in oncology. JAMA 1999; 282(15): 1453–7

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank the following clinical experts for their input during the expert panel meetings: Dr Mario Di Palma (France); Dr Gunter von Minckwitz (Germany); Dr Jalid Sehouli (Germany); Dr Marco Danova (Italy); Dr Sergio Palmeri (Italy); Dr Jose Ignacio Mayordomo (Spain); Dr Antonio Lopez Pousa (Spain) and Dr Robert Leonard (UK). We would also like to thank Dr Robert W. Dubois, Chief Medical Officer of Cerner LifeSciences, for his clinical insights regarding the model and contributions to the manuscript, and Philip Booth, formerly with Amgen UK, for his assistance with data collection.

This study was funded by Amgen (Europe) GmbH. At the time of the research, Dr Liu was employed by Cerner LifeSciences, which provides consulting services to the pharmaceutical industry. Dr Doan was also employed by Cerner Life-Sciences at the time of this study. Dr Malin was an employee of Amgen Inc. at the time the research. Dr Leonard has provided consulting to Amgen, served on advisory boards for Amgen, and received honoraria and an educational grant from the company. He has also spoken at Amgen-sponsored meetings.

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Authors and Affiliations

  1. Cerner LifeSciences, Cerner Corporation, 9100 Wilshire Blvd, Suite 655E, Beverly Hills, CA, 90212, USA

    Zhimei Liu & Quan V. Doan

  2. David Geffen School of Medicine at UCLA, Los Angeles, California, USA

    Jennifer Malin

  3. Imperial College NHS Trust, London, UK

    Robert Leonar

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  1. Zhimei Liu
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Correspondence to Zhimei Liu.

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Liu, Z., Doan, Q.V., Malin, J. et al. The economic value of primary prophylaxis using pegfilgrastim compared with filgrastim in patients with breast cancer in the UK. Appl Health Econ Health Policy 7, 193–205 (2009). https://doi.org/10.1007/BF03256152

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