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Cost Effectiveness and Cost Utility of Adjuvant Interferon α in Cutaneous Melanoma

A Review

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Abstract

Although interferon α (IFN) has been approved since 1995 in the US as adjuvant therapy for high-risk melanoma patients, its cost effectiveness and economic value have only been recently addressed. There are very few papers that address the overall cost and cost components of treating melanoma patients, all of them focusing on the US. These studies showed the large cost of treatment of stage III and IV patients (around $US40 000–60 000 [1997/8 values]). Chemotherapy and adjuvant immunomodulators comprised a large part of this cost.

Cost-effectiveness studies performed for the US, Spain and Italy have been largely based on the results of the pivotal Eastern Cooperative Oncology Group (ECOG) 1684 trial using high-dose (10–20 Megaunits [MU]/m2) IFN in mainly stage III patients. Incremental cost-effectiveness ratios for adjuvant IFN versus observation from these studies fall in the range of $US13 000–40 000 per life-year gained (1998 values), depending on the time horizon, discount rate and cost of IFN, with an extrapolated life-gain over lifetime ranging between 1.9 and 3 years.

Only one study, the French Cooperative Melanoma Group trial in stage IIA/B patients, used low-dose (3 MU2) IFN and yielded a quite favourable incremental cost effectiveness ratio (cost per life-year gained) ranging from $US12 954 over 5 years (survival gain 3 months) to $US1544 over a lifetime (extrapolated survival gain 2.6 years) [1995 values].

Although these results could be seen as supporting the more widespread use of adjuvant IFN in melanoma, it should be stressed that they were based on the only two positive clinical trials out of a total of ten. Moreover, the impact on survival was lost in both positive trials at ≥8 years’ follow-up and thus the costs assessments are likely to be overly optimistic. The eight negative high-dose (HDI) and low-dose (LDI) IFN trials have failed to show an impact on survival (HDI: ECOG 1690 and North Central Cancer Treatment Group [NCCTG]; LDI: ECOG 1690, WHO-16, UK Coordinating Committee on Cancer Research [UKCCRC] and Austrian, Scottish and European Organisation for Research and Treatment of Cancer trials).

Mature results from more recent trials are pending. A definitive appraisal of the cost effectiveness of IFN in melanoma patients will have to await these results and their economic analyses.

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  1. A refusal vote is where people have a negatively coloured view. People are so afraid of the word ‘cancer’ that whatever situation is linked with cancer receives a very low value because people do not want to hear about it.

References

  1. Bray F, Sankila R, Ferlay J, et al. Estimates of cancer incidence and mortality in Europe in 1995. Eur J Cancer 2002; 38: 99–166

    Article  PubMed  CAS  Google Scholar 

  2. Balch MC, Buzaid CA, Soong S-J, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19 (16): 3635–48

    PubMed  CAS  Google Scholar 

  3. Balch MC, Soong S-J, Gershenwald EJ, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001; 19 (16): 3622–34

    PubMed  CAS  Google Scholar 

  4. AJCC comparison guide cancer staging manual, 5th versus 6th ed. Chicago (IL): American Joint Committee on Cancer, 2002

  5. Tsao H, Rogers SG, Sober JA. An estimate of the annual direct cost of treating cutaneous melanoma. J Am Acad Dermatol 1998; 38: 669–80

    Google Scholar 

  6. Eggermont AMM, Gore M. European approach to adjuvant treatment of intermediate and high risk malignant melanoma. Semin Oncol 2002; 29 (4): 382–8

    Article  PubMed  Google Scholar 

  7. McClay EF. Adjuvant therapy for patients with high-risk malignant melanoma. Semin Oncol 2002; 29: 389–99

    Article  PubMed  Google Scholar 

  8. Spitler LE. Adjuvant therapy of melanoma. Oncology 2002; 16 (1 Suppl. 1): 40–8

    PubMed  Google Scholar 

  9. Kirkwood JM, Strawderman MH, Ernstroff MS, et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996 Jan; 14 (1): 7–17

    PubMed  CAS  Google Scholar 

  10. Cascinelli N, Belli F, MacKie RM, et al. Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial. Lancet. 2001 Sep 15; 358 (9285): 866–9

    Article  PubMed  CAS  Google Scholar 

  11. Grob JJ, Dreno B, de la Salmonière P, et al. Randomised trial of interferon alfa-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet 1998 Jun 27; 351 (9120): 1905–10

    Article  PubMed  CAS  Google Scholar 

  12. Pehamberger H, Soyer HP, Steiner A, et al. Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma.Austrian Malignant Melanoma Cooperative Group. J Clin Oncol. 1998 Apr; 16 (4): 1425–9

    PubMed  CAS  Google Scholar 

  13. Cameron DA, Cornbleet MC, Mackie RM, et al. Adjuvant interferon alpha 2b in high risk melanoma – the Scottish study. Br J Cancer. 2001 May 4; 84 (9): 1146–9

    Article  PubMed  CAS  Google Scholar 

  14. Punt CJ, Eggermont AM. Adjuvant interferon-alpha for melanoma revisited: news from old and new studies. Ann Oncol 2001 Dec; 12 (12): 1663–6

    Article  PubMed  CAS  Google Scholar 

  15. Hancock BW, Wheatley K, Harris S, et al. Adjuvant interferon in high-risk melanoma: the AIM HIGH Study – United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma. J Clin Oncol. 2004 Jan 1; 22(1): 53–61

    Article  PubMed  CAS  Google Scholar 

  16. Eggermont AMM. The role IFN-alpha in malignant melanoma remains to be defined. Eur J Cancer 2001; 37: 2147–53

    Article  PubMed  CAS  Google Scholar 

  17. Lens MB, Dawes M. IFN alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 2002 Apr 1; 20 (7): 1818–25

    Article  PubMed  CAS  Google Scholar 

  18. Kirkwood JM. Melanoma. In: DeVita Jr VT, Hellman S, Rosenberg SA, editors. Biologic therapy of cancer: principles and practice. Phildelphia (PA): JB Lippincott, 1995: 388–411

    Google Scholar 

  19. Slaton JW, Perrotte P, Inoue K, et al. IFN-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin Cancer Res 1999; 5: 2726–34

    PubMed  CAS  Google Scholar 

  20. Kirkwood JM, Manola J, Ibrahim J, et al. A pooled analysis of lifeeastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res 2004 Mar 1; 10 (5): 1670–7

    Article  PubMed  CAS  Google Scholar 

  21. Kirkwood JM. Efficacy and safety of high-dose IFNá-2b in patients with high-risk resected cutaneous melanoma; presentation at NCI/CBER 3/08/2002 [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/02/slides/3838s1_01_cber/ [Accessed 2003 Jun 26]

  22. Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose IFN alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 2000; 18: 2444–59

    PubMed  CAS  Google Scholar 

  23. Kirkwood JM, Manola J, Ibrahim JG, et al. Pooled analysis of four ECOG EST-Intergroup trials of high-dose IFN alfa-2b (HDI) in 1916 patients with high-risk resected cutaneous melanoma [abstract]. Proc Am Soc Clin Oncol 2001; 20: 1395

    Google Scholar 

  24. Lafuma A, Dreno B, Delaunay M, et al. Economic analysis of adjuvant therapy with IFN alpha-2a in stage II malignantc melanoma. Eur J Cancer 2001; 37: 369–75

    Google Scholar 

  25. Wheatley K, Hancock B, Gore M, et al. IFN-α as adjuvant therapy for melanoma: a meta-analysis of the randomised trials [abstract]. Proc Am Soc Clin Oncol 2001; 20: 1394

    Google Scholar 

  26. Hillner EB, Kirkwood MJ, Agarwala SS. Burden of illness associated with metastatic melanoma: an audit of 100 consecutive referral center cases. Cancer 2001; 91: 1814–21

    Article  PubMed  CAS  Google Scholar 

  27. Gelber RD, Goldhirsch A, Cavalli F. Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast cancer. The International Breast Cancer Study Group. Ann Intern Med 1991 Apr 15; 114 (8): 621–8

    PubMed  CAS  Google Scholar 

  28. Cole FB, Gelber DR, Kirkwood MJ, et al. Quality-of-life-adjusted survival analysis of IFN alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: An Eastern cooperative oncology group study. J Clin Oncol 1996; 14: 2666–73

    PubMed  CAS  Google Scholar 

  29. Kilbridge LK, Weeks CJ, Sober JA, et al. Patient preferences for adjuvant IFN alpha-2B treatment. J Clin Oncol 2001; 19: 812–23

    PubMed  CAS  Google Scholar 

  30. Crott R, Ali F, Burdette-Radoux S. Measurement of utilitybased quality-of-life in adjuvant IFN therapy in melanoma [abstract]. Qual Life Res 1999; 8: 284

    Google Scholar 

  31. Dolan P. Output measures and valuation in health. In: Drummond M, McGuire A, editors. Economic evaluation in health care. Oxford: Oxford University Press, 2001

    Google Scholar 

  32. Kilbridge KL, Cole BF, Kirkwood JM, et al. Quality-of-life-32. Kilbridge KL, Cole BF, Kirkwood JM, et al. Quality-of-life data. J Clin Oncol 2002; 20 (5): 1311–8

    Article  PubMed  CAS  Google Scholar 

  33. Brown JE, King MT, Butow PN, et al. Patterns over time in quality of life, coping and psychological adjustment in late stage melanoma patients: an application of multilevel models. Qual Life Res 2001; 9: 75–85

    Article  Google Scholar 

  34. Hillner EB, Kirkwood JM, Atkins BM, et al. Economic analysis of adjuvant IFN alfa-2B in high-risk melanoma based on projections from Eastern cooperative group 1684. J Clin Oncol 1997; 15: 2351–8

    Google Scholar 

  35. Hillner EB. Cost-effectiveness assessment of IFN alpha-2b as adjuvant therapy of high-risk resected cutaneous melanoma. Eur J Cancer 1998; 34 Suppl. 3: S18–21

    Google Scholar 

  36. Slingluff CL, Dodge RK, Stanley WE, et al. The annual risk of melanoma progression: implications for the concept of cure. Cancer 1992; 70 (7): 1917–27

    Article  PubMed  Google Scholar 

  37. Messori A, Becagli P, Trippoli S, et al. A retrospective cost-effectiveness analysis of IFN as adjuvant therapy in high-risk resected cutaneous melanoma. Eur J Cancer 1997; 33: 1373–9

    Article  PubMed  CAS  Google Scholar 

  38. Gonz´alez-Larriba JL, Serrano S, Alvarez-Mon M, et al. Cost-effectiveness analysis of interferon as adjuvant therapy in high-risk melanoma patients in Spain. Eur J Cancer 2000; 36: 2344–52

    Article  Google Scholar 

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Acknowledgements

The author has no conflicts of interest directly relevant to the content of this review and no funding from pharmaceutical companies was used in completing the review.

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Crott, R. Cost Effectiveness and Cost Utility of Adjuvant Interferon α in Cutaneous Melanoma. PharmacoEconomics 22, 569–580 (2004). https://doi.org/10.2165/00019053-200422090-00002

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