Applied Health Economics and Health Policy

, Volume 11, Issue 1, pp 27–43 | Cite as

A Systematic Review of Economic Evaluations in Second and Later Lines of Therapy for the Treatment of Non-Small Cell Lung Cancer

  • Anne Jäkel
  • Melanie Plested
  • Kuntal Dharamshi
  • Rakhee Modha
  • Sarah Bridge
  • Adam Johns
Systematic Review

Abstract

Introduction

Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Surgery is generally accepted as the first-line treatment in patients with advanced/metastatic NSCLC, followed by radiotherapy and chemotherapy as second-line treatments. Docetaxel or erlotinib are generally recommended as the first-line chemotherapy option. The objective of this review was to identify previously published economic evaluations in NSCLC for second- and later-line treatments in order to (i) determine common modelling approaches and (ii) establish the relative cost effectiveness of these treatments. An overview of model critique was also produced to identify common criticisms from health technology assessment (HTA) bodies on the models submitted.

Methods

MEDLINE, Embase, EconLit, MEDLINE in Process® and NHS Economic Evaluation Database (NHSEED) were searched (database start–October 2011), along with proceedings from eight major conferences (2007–2011). National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (PBAC) and Canadian Agency for Drugs and Technologies in Health (CADTH) websites and the International Network of Agencies for Health Technology Assessment (INAHTA) database were also searched for appraisals in second- or later-line NSCLC. All published studies and HTA appraisals that reported economic evaluations of interventions used in current clinical practice as second- or later-line treatment in patients with advanced/metastatic NSCLC were included. Only studies in English were considered for inclusion. Studies which met the eligibility criteria after the screening of full-text articles were extracted by a reviewer and checked by a second party. Where multiple publications were identified describing a single study, the extracted data were compiled into one entry.

Results

A total of 29 studies were included which clearly evaluated second-line or later-line regimens. Most studies were either cost-effectiveness or cost-utility evaluations. Three-state transition Markov models were frequently used in cost-effectiveness and cost-utility evaluations. The model inputs were well reported and commonly consisted of data from pivotal trials. Sensitivity analyses were conducted in the majority of studies and covered variables such as cost, effectiveness, hospitalization and treatment duration. Therapies (docetaxel, pemetrexed and erlotinib) are for the most part cost-effective/cost-saving second-line therapies compared with best supportive care (BSC). Six erlotinib HTAs, across NICE, SMC, and PBAC, and four pemetrexed HTAs, one by NICE and three by SMC, were identified. The CADTH website did not provide sufficient detail on the appraisals and was excluded. Certain aspects of the models and model assumptions, e.g. efficacy inputs, were criticized or determined unjustifiable by the NICE, SMC and PBAC appraisal committees. Erlotinib and pemetrexed were considered to be cost effective versus docetaxel by NICE and SMC in the final submissions. PBAC considered erlotinib to be cost effective versus BSC following a price reduction in 2008.

Conclusion

Three-state Markov models are often used to conduct economic analysis in NSCLC and are regarded as appropriate to HTA agencies. Docetaxel, erlotinib and BSC are suitable comparators that should be considered for use in the model in the UK and Australia. Further, manufacturers should carefully select underlying assumptions used in the model, for both costs and clinical inputs, where the latter is derived from direct head-to-head trial data.

Notes

Acknowledgments

The authors also acknowledge the contribution of Seema Patel from Heron Evidence Development Ltd for contributing to the analysis of the data, and of the Indian team of Heron Evidence Development Pvt Ltd for the collation and reporting of review evidence.

Financial disclosure

This study was sponsored by Pfizer. Anne Jäkel, Kuntal Dharamshi, Melanie Plested and Rakhee Modha are current employees of Heron Evidence Development Ltd, who were paid consultants to Pfizer in connection with the development of this manuscript, and provided editorial/medical writing support which was funded by Pfizer.

Author contributions

Adam Johns (a current employee of Pfizer) and Sarah Bridge (an employee of Pfizer at the time this analysis was carried out) substantially contributed to the analysis and interpretation of data and reviewed and approved the manuscript. Anne Jakel acts as guarantor for the overall content.

Supplementary material

40258_2012_1_MOESM1_ESM.pdf (21 kb)
Supplementary material 1 (PDF 21 kb)

References

  1. 1.
    Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008, Cancer incidence and mortality worldwide: IARC CancerBase No. 10 [online]. http://globocan.iarc.fr/. Accessed 2010 Nov 03.
  2. 2.
    Cancer Research UK. Lung cancer and smoking statistics: key facts [online]. http://www.cancerresearchuk.org/cancer-info/cancerstats/keyfacts/lung-cancer/. Accessed 2010 Nov 05.
  3. 3.
    Cancer Research UK. UK cancer incidence statistics for common cancers [online]. http://info.cancerresearchuk.org/cancerstats/incidence/commoncancers/. Accessed 2009 Feb 01.
  4. 4.
    Chouaid C, Atsou K, Hejblum G, et al. Economics of treatments for non-small cell lung cancer. Pharmacoeconomics. 2009;27(2):113–25.PubMedCrossRefGoogle Scholar
  5. 5.
    Kutikova L, Bowman L, Chang S, et al. The economic burden of lung cancer and the associated costs of treatment failure in the United States. Lung Cancer. 2005;50(2):143–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Carlson JJ, Veenstra DL, Ramsey SD. Pharmacoeconomic evaluations in the treatment of non-small cell lung cancer. Drugs. 2008;68(8):1105–13.PubMedCrossRefGoogle Scholar
  7. 7.
    Clegg A, Scott DA, Hewitson P, et al. Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review. Thorax. 2002;57(1):20–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Lyseng-Williamson KA. Erlotinib: a pharmacoeconomic review of its use in advanced non-small cell lung cancer. Pharmacoeconomics. 2010;28(1):75–92.PubMedCrossRefGoogle Scholar
  9. 9.
    Waters JS, O’Brien ME. The case for the introduction of new chemotherapy agents in the treatment of advanced non small cell lung cancer in the wake of the findings of The National Institute of Clinical Excellence (NICE). Br J Cancer. 2002;87(5):481–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ. 1996;313(7052):275–83.PubMedCrossRefGoogle Scholar
  11. 11.
    Philips Z, Bojke L, Sculpher M, et al. Good practice guidelines for decision-analytic modelling in health technology assessment: a review and consolidation of quality assessment. Pharmacoeconomics. 2006;24(4):355–71.PubMedCrossRefGoogle Scholar
  12. 12.
    Clegg A, Scott DA, Sidhu M, et al. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer. Health Technol Assess. 2001;5(32):1–195.Google Scholar
  13. 13.
    Holmes J, Dunlop D, Hemmett L, et al. A cost-effectiveness analysis of docetaxel in the second-line treatment of non-small cell lung cancer. Pharmacoeconomics. 2004;22(9):581–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Bhalla S, Hibbert C, Watkins J, et al. To determine the cost-effectiveness of pemetrexed (PEM) compared to current standards of care in 2nd-line advanced non-small cell lung cancer (NSCLC) from the UK National health Service (NHS) perspective [abstract]. J Clin Oncol. 2007;25(18 Suppl):6540.Google Scholar
  15. 15.
    Lewis G, Peake M, Aultman R, et al. Cost-effectiveness of erlotinib versus docetaxel for second-line treatment of advanced non-small-cell lung cancer in the United Kingdom. J Int Med Res. 2010;38(1):9–21.PubMedCrossRefGoogle Scholar
  16. 16.
    Rutkowski J, Gwiosda B, Lisiecka B, et al. Cost-utility of docetaxel compared with best supportive care and pemetrexed in second line treatment of non-small cell lung cancer in Poland [abstract PCN120]. In: 12th Annual European Congress, ISPOR, 2009 Oct 24–Oct 27, Paris.Google Scholar
  17. 17.
    Capri S, Morabito A, Carillio G, et al. Economic evaluation of erlotinib, docetaxel and pemetrexed as second line treatment in patients with advanced non-small-cell lung cancer (NSCLC): a cost-minimisation in Italian hospitals [abstract PCN36]. Value Health 2007;10 (s1):A333.Google Scholar
  18. 18.
    Asukai Y, Valladares A, Camps C, et al. Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population. BMC Cancer. 2010;10:26.PubMedCrossRefGoogle Scholar
  19. 19.
    Vergnenegre A, Corre R, Berard H, et al. An economical, randomized, multicenter phase III trial of second line treatment for non small cell lung cancer (NSCLC) comparing docetaxel versus pemetrexed: GFPC (Groupe Francnullais De pneumo-cancerologie) 05–06 study [abstract]. Value Health. 2009;12(7):A281.CrossRefGoogle Scholar
  20. 20.
    Vergnenegre A, Corre R, Berard H, et al. Cost-effectiveness of second-line chemotherapy for non-small cell lung cancer: an economic, randomized, prospective, multicenter phase III trial comparing docetaxel and pemetrexed: the GFPC 05–06 study. J Thorac Oncol. 2011;6(1):161–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Kotowa W, Gatzemeier U, Pirk O, et al. A comparison of the estimated costs of erlotinib, docetaxel and pemetrexed for the second-line treatment of non-small cell lung cancer from the German healthcare perspective. J Med Econ. 2007;10(3):255–71.CrossRefGoogle Scholar
  22. 22.
    Suchankova E, Dolezal T. Cost-minimisation analysis of erlotinib versus docetaxel or pemetrexed as a second-line treatment of advanced non-small lung (NSCLC) in the conditions of the Czech Republic [abstract no. PCN50]. In: 11th Annual European Congress, ISPOR 2008 Nov 9, Athens.Google Scholar
  23. 23.
    Leighl NB, Shepherd FA, Kwong R, et al. Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer. J Clin Oncol. 2002;20(5):1344–52.PubMedCrossRefGoogle Scholar
  24. 24.
    Leighl NB, Shepherd FA, Kwong R, et al. Economic analysis of TAX 317: docetaxel vs. best supportive care (BSC) for second line management of advanced non-small cell lung cancer (NSCLC) [abstract no. 1291]. Proc Am Soc Clin Oncol 2001; 20.Google Scholar
  25. 25.
    Cromwell I, van der Hoek K. MBPS. Erlotinib vs docetaxel as second-line treatment of advanced NSCLC: a real-world cost-effectiveness study [abstract no. P3.036]. In: 14th World conference on lung cancer, 2011 Jul 3–7, Amsterdam.Google Scholar
  26. 26.
    Hsia T, Chang G, Chen Y, et al. Pharmacoeconomic analysis of erlotinib as second-line treatment of advanced non-small cell lung cancer in Taiwan [abstract]. In: 14th European cancer conference, ECCO, 2007 Sept 23–27, Barcelona [J Cancer 2007;5 (4 Suppl):357].Google Scholar
  27. 27.
    Hsia T, Chang G, Chen Y, et al. Cost-effectiveness analysis of erlotinib compared with docetaxel and pemetrexed for second-line treatment of advanced non-small cell lung cancer (NSCLC) in Taiwan [abstract]. In: 10th Annual European Congress, ISPOR; 2007 Oct 20–23, Dublin [Value Health 2007;10 (6):A325].Google Scholar
  28. 28.
    Anaya P, Lopez RJ, Polanco AC. Cost-utility analysis of gefitinib versus docetaxel in a Mexican public institution [abstract]. In: ISPOR 14th annual international meeting; 2009 Oct 24–27, Orlando, FL.Google Scholar
  29. 29.
    Thongprasert S, Permsuwan U. Cost-effectiveness and budget impact analyses of gefitinib in 2nd-line treatment for advanced NSCLC from Thai payer perspective [abstract]. Ann Oncol 2010;21:viii345.Google Scholar
  30. 30.
    Yu YF, Chen ZW, Zhou Z, et al. A cost-effectiveness analysis of docetaxel versus pemetrexed in second-line chemotherapy for stage IIIb or IV non-small cell lung cancer in China. Chemotherapy. 2010;56(6):472–7.PubMedCrossRefGoogle Scholar
  31. 31.
    McLeod C, Bagust A, Boland A, et al. Erlotinib for the treatment of relapsed non-small cell lung cancer. Health Technol Assess. 2009;13(Suppl 1):41–7.PubMedGoogle Scholar
  32. 32.
    Rubio-Terres C, Alvarez Sanz C, Gylmark GM. Pharmacoeconomic analysis in Spain of therapy with erlotinib, docetaxel, pemetrexed or best supportive care in patients with advanced non-small cell lung cancer who have failed previous chemotherapy regimens [abstract]. In: 11th Annual European Congress, ISPOR 2008 Nov 8–11, Athens [Value Health 2006 Nov; 9 (6):A283].Google Scholar
  33. 33.
    Araujo A, Parente B, Sotto-Mayor R, et al. An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer. Rev Port Pneumol. 2008;14(6):803–27.PubMedGoogle Scholar
  34. 34.
    Negreiro F, Pereira C, Pereira H, et al. Economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as 2nd or 3rd line treatment of non-small-cell lung cancer [PCN52]. In: 11th Annual European Congress, ISPOR, 2008 Nov 1, Athens.Google Scholar
  35. 35.
    Pompen M, Novak A, Postmus P, et al. Pharmacoeconomic (PE) analysis of the treatment of non-small cell lung cancer (NSCLC) in the Netherlands demonstrates that erlotinib dominates docetaxel and is cost-effective over best supportive care (BSC) without need for patient stratification [abstract]. In: 9th Annual European Congress, ISPOR 2006 Oct 29–31, Copenhagen [Value Health; 9 (6):A203].Google Scholar
  36. 36.
    Ciuleanu TE, Dediu M, Minea LN, et al. Cost-effectiveness analysis of erlotinib in the treatment of advanced non-small cell lung cancer (NSCLC) in Romania. In: 15th Annual International Meeting, ISPOR; 2010 May 15–19, Atlanta [Value Health; 13 (3):A38].Google Scholar
  37. 37.
    Batigun O, Yildirim E. Pharmacoeconomic analysis of erlotinib compared with docetaxel for the treatment of relapsed non-small-cell lung cancer (NSCLC) in Turkey [abstract]. In: 10th Annual European Congress, ISPOR, 2007 Oct 20–23, Dublin [Value Health; 10 (6):A234].Google Scholar
  38. 38.
    Carlson JJ, Reyes C, Oestreicher N, et al. Comparative clinical and economic outcomes of treatments for refractory non-small cell lung cancer (NSCLC). Lung Cancer. 2008;61(3):405–15.PubMedCrossRefGoogle Scholar
  39. 39.
    Horgan AM, Bradbury PA, Amir E, et al. An economic analysis of the INTEREST trial, a randomized trial of docetaxel versus gefitinib as second-/third-line therapy in advanced non-small-cell lung cancer. Ann Oncol. 2011;22(8):1805–11.PubMedCrossRefGoogle Scholar
  40. 40.
    Horgan A, Shepherd F, Bradbury P, et al. Preliminary cost-consequence analysis of the INTEREST trial, a randomized trial of docetaxel versus gefitinib as 2nd line therapy in advanced non-small cell lung cancer [abstract 8110]. ASCO Annual Meeting 2008. J Clin Oncol. 2008;26(15 Suppl.):8110.Google Scholar
  41. 41.
    Cromwell I, van der Hoek K, Taylor S, et al. Erlotinib vs best supportive care as third-line treatment of advanced NSCLC: a real-world cost-effectiveness study [abstract no. P3.110]. In: 14th World conference on lung cancer, 2011 Jul 3–7, Amsterdam.Google Scholar
  42. 42.
    Bradbury P, Jang R, Isogai P, et al. A cost utility analysis of erlotinib in patients with previously treated advanced non-small-cell lung cancer (NSCLC) [abstract]. In: 13th Annual international meeting, ISPOR, 2008 May 3–7, Toronto.Google Scholar
  43. 43.
    Bradbury PA, Tu D, Seymour L, et al. Economic analysis: randomized placebo-controlled clinical trial of erlotinib in advanced non-small cell lung cancer. J Natl Cancer Inst. 2010;102(5):298–306.PubMedCrossRefGoogle Scholar
  44. 44.
    Stefani SD, Saggia MG, dos Santos EAV. Cost-minimisation analysis of erlotinib in the second-line treatment of non-small-cell lung cancer: a Brazilian perspective. J Med Econ. 2008;11(3):383–96.CrossRefGoogle Scholar
  45. 45.
    Stefani S, Saggia M, Santos E. Cost-minimisation analysis of erlotinib versus docetaxel or pemetrexed as second-line therapy for non-small cell lung cancer (NSCLC) from the perspective of a private payer in Brazil [abstract PCN32]. In: ISPOR 10th Annual European Congress, 2007 Oct 20–23, Dublin.Google Scholar
  46. 46.
    Santos E, Stefani M, Saggia M. Cost-minimisation analysis of erlotinib versus docetaxel or pemetrexed as second-line therapy for non-small cell lung cancer (NSCLC) from the perspective of a private payer in Brazil according to local HTA guidelines. In: 33rd Annual ESMO Meeting, 2008 Sep 12–16, Stockholm.Google Scholar
  47. 47.
    Pavlakis N, Mitchell PL, Stynes G, et al. Cost-effectiveness of pemetrexed for previously treated advanced non-small cell lung cancer [abstract]. ASCO Annual meeting proceedings: Part I of II. J Clin Oncol. 2005;23(165 Suppl):6084.Google Scholar
  48. 48.
    Kim YG, Lee EK. Cost-effectiveness analysis of erlotinib versus docetaxel as a second-or third-line treatment of non-small cell lung cancer in Korea [abstract]. Value Health. 2010;13(7):A514.CrossRefGoogle Scholar
  49. 49.
    National Institute for Health and Clinical Excellence. Pemetrexed for the treatment of non-small cell lung cancer: report no.: TA124. National Institute for Health and Clinical Excellence; 2007.Google Scholar
  50. 50.
    Scottish Medicines Consortium. Erlotinib, 25, 100 and 150 mg film-coated tablets (220/05): NHS Scotland; 2005. Report No.: 220/05.Google Scholar
  51. 51.
    Scottish Medicines Consortium. Erlotinib, 100 and 150 mg film-coated tablets, resubmission (220/05): NHS Scotland; 2006. Report No.: Resubmission 220-05.Google Scholar
  52. 52.
    Scottish Medicines Consortium. Pemetrexed, 500 mg, powder for reconstitution (342/07): NHS Scotland; 2007. Report No.: 342/07.Google Scholar
  53. 53.
    Scottish Medicines Consortium. Pemetrexed, 500 mg vial of powder for solution for intravenous infusion (342/07), first resubmission: NHS Scotland; 2008.Google Scholar
  54. 54.
    Scottish Medicines Consortium. Pemetrexed 500 mg vial of powder for solution for intravenous infusion, second resubmission (342/07): NHS Scotland; 2008.Google Scholar
  55. 55.
    Pharmaceutical Benefits Advisory Committee. Erlotinib hydrochloride, film-coated tablets, 25 mg, 100 mg, 150 mg (base), Tarceva®: PBAC; 2007 Nov.Google Scholar
  56. 56.
    Pharmaceutical Benefits Advisory Committee. Erlotinib hydrochloride, film-coated tablets, 25 mg, 100 mg, 150 mg (base), Tarceva®: PBAC; 2006 Nov.Google Scholar
  57. 57.
    Pharmaceutical Benefits Advisory Committee. Erlotinib hydrochloride, film-coated tablets, 25 mg, 100 mg, 150 mg (base), Tarceva®: PBAC; 2006 March.Google Scholar
  58. 58.
    National Institute for Health and Clinical Excellence. Erlotinib for the treatment of non-small-cell lung cancer: National Institute for Health and Clinical Excellence; 2008 Oct. Report No.: TA162.Google Scholar
  59. 59.
    National Institute for Health and Clinical Excellence. Gefitinib for the second-line treatment of locally advanced or metastatic non-small-cell lung cancer (terminated appraisal): National Institute for Health and Clinical Excellence; 2009. Report No.: TA175.Google Scholar
  60. 60.
    National Institute for Health and Clinical Excellence. Lung cancer (non-small-cell, second line treatment)-vandetanib (suspended): National Institute for Health and Clinical Excellence; 2008. Report No.: TA Wave19/54.Google Scholar
  61. 61.
    Canadian Coordinating Office for Health Technology Assessment. Erlotinib. Tarceva-Hoffmann-La Roche Limited: CCOHTA; 2005 Dec 6.Google Scholar
  62. 62.
    Canadian Coordinating Office for Health Technology Assessment. Gefitinib 250 mg tablets (Iressa: AstraZeneca): CCOHTA; 2004 Jun 23.Google Scholar
  63. 63.
    Appleby J, Devlin N, Parkin D. NICE’s cost effectiveness threshold. BMJ. 2007;335(7616):358–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Gold M, Siegel J, Russell L. Cost-effectiveness in health and medicine: report of the panel on cost-effectiveness in health and medicine. New York, NY: Oxford University Press; 1996.Google Scholar
  65. 65.
    Mather D, Sullivan SD, Parasuraman TV. Beyond survival: economic analyses of chemotherapy in advanced, inoperable NSCLC. Oncology. 1998;12(2):199–209.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  • Anne Jäkel
    • 1
  • Melanie Plested
    • 1
  • Kuntal Dharamshi
    • 1
  • Rakhee Modha
    • 1
  • Sarah Bridge
    • 2
  • Adam Johns
    • 2
  1. 1.Heron Evidence Development LtdLutonUK
  2. 2.Pfizer LtdSurreyUK

Personalised recommendations