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Published in: PharmacoEconomics 7/2018

01-07-2018 | Original Research Article

Economic Analysis of First-Line Treatment with Cetuximab or Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer in England

Authors: Irina A. Tikhonova, Nicola Huxley, Tristan Snowsill, Louise Crathorne, Jo Varley-Campbell, Mark Napier, Martin Hoyle

Published in: PharmacoEconomics | Issue 7/2018

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Abstract

Background

Combination therapies with cetuximab (Erbitux®; Merck Serono UK Ltd) and panitumumab (Vectibix®; Amgen UK Ltd) are shown to be less effective in adults with metastatic colorectal cancer who have mutations in exons 2, 3 and 4 of KRAS and NRAS oncogenes from the rat sarcoma (RAS) family.

Objective

The objective of the study was to estimate the cost effectiveness of these drugs in patients with previously untreated RAS wild-type (i.e. non-mutated) metastatic colorectal cancer, not eligible for liver resection at baseline, from the UK National Health Service and Personal Social Services perspective.

Methods

We constructed a partitioned survival model to evaluate the long-term costs and benefits of cetuximab and panitumumab combined with either FOLFOX (folinic acid, fluorouracil and oxaliplatin) or FOLFIRI (folinic acid, fluorouracil and irinotecan) vs. FOLFOX or FOLFIRI alone. The economic analysis was based on three randomised controlled trials. Costs and quality-adjusted life-years were discounted at 3.5% per annum.

Results

Based on the evidence available, both drugs fulfil the National Institute for Health and Care Excellence’s end-of-life criteria. In the analysis, assuming discount prices for the drugs from patient access schemes agreed by the drug manufacturers with the Department of Health, predicted mean incremental cost-effectiveness ratios for cetuximab + FOLFOX, panitumumab + FOLFOX and cetuximab + FOLFIRI compared with chemotherapy alone appeared cost-effective at the National Institute for Health and Care Excellence’s threshold of £50,000 per quality-adjusted life-year gained, applicable to end-of-life treatments.

Conclusion

Cetuximab and panitumumab were recommended by the National Institute for Health and Care Excellence for patients with previously untreated RAS wild-type metastatic colorectal cancer, not eligible for liver resection at baseline, for use within the National Health Service in England. Both treatments are available via the UK Cancer Drugs Fund.
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Literature
6.
go back to reference Merck Serono. Summary of product characteristics: Erbitux (cetuximab). Feltham, UK: Merck Serono; 2014. Merck Serono. Summary of product characteristics: Erbitux (cetuximab). Feltham, UK: Merck Serono; 2014.
7.
go back to reference Amgen Ltd. Summary of product characteristics: Vectibix (panitumumab). Cambridge: Amgen Ltd; 2014. Amgen Ltd. Summary of product characteristics: Vectibix (panitumumab). Cambridge: Amgen Ltd; 2014.
9.
go back to reference Goodsell DS. The molecular perspective: the ras oncogene. Oncologist. 1999;4(3):263–4.PubMed Goodsell DS. The molecular perspective: the ras oncogene. Oncologist. 1999;4(3):263–4.PubMed
11.
go back to reference Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25:1346–55.CrossRefPubMed Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25:1346–55.CrossRefPubMed
13.
go back to reference Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–7.CrossRefPubMed Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–7.CrossRefPubMed
14.
go back to reference European Medicines Agency. Cetuximab (Erbitux): summary of opinion (post authorisation). London: European Medicines Agency; 2011. European Medicines Agency. Cetuximab (Erbitux): summary of opinion (post authorisation). London: European Medicines Agency; 2011.
15.
go back to reference European Medicines Agency. Panitumumab (Vectibix): summary of opinion (post authorisation). London: European Medicines Agency; 2011. European Medicines Agency. Panitumumab (Vectibix): summary of opinion (post authorisation). London: European Medicines Agency; 2011.
16.
go back to reference European Medicines Agency. Cetuximab (Erbitux) assessment report (variation assessment report; EMEA/h/C/000558/II/0062). London: European Medicines Agency; 2013. European Medicines Agency. Cetuximab (Erbitux) assessment report (variation assessment report; EMEA/h/C/000558/II/0062). London: European Medicines Agency; 2013.
17.
go back to reference European Medicines Agency. Panitumumab (Vectibix) assessment report (variation assessment report; EMEA/H/C/000741/II/0050). London: European Medicines Agency; 2013. European Medicines Agency. Panitumumab (Vectibix) assessment report (variation assessment report; EMEA/H/C/000741/II/0050). London: European Medicines Agency; 2013.
20.
go back to reference National Institute for Health and Care Excellence. Technology appraisal 176 (TA176): cetuximab for the first-line treatment of metastatic colorectal cancer. London: NICE; 2009. National Institute for Health and Care Excellence. Technology appraisal 176 (TA176): cetuximab for the first-line treatment of metastatic colorectal cancer. London: NICE; 2009.
21.
go back to reference NHS England. Cancer drugs fund decision summary: panitumumab: treatment of adult patients with wild-type RAS (KRAS and NRAS) metastatic colorectal cancer (mCRC) in first-line in combination with FOLFOX. London: NHS England; 2014. Available from: https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&ved=0ahUKEwjV8v2m4rPVAhVpJcAKHXWCBVgQFggwMAI&url=https%3A%2F%2Fwww.nice.org.uk%2Fguidance%2Fta240%2Fdocuments%2Fcolorectal-cancer-metastatic-panitumumab-terminated-appraisal-appendix-b-ge-proposal-paper-january-20152&usg=AFQjCNFLNQSDzjhnmBQESt9XA7YRfoT9hg. Accessed 20 Feb 2018. NHS England. Cancer drugs fund decision summary: panitumumab: treatment of adult patients with wild-type RAS (KRAS and NRAS) metastatic colorectal cancer (mCRC) in first-line in combination with FOLFOX. London: NHS England; 2014. Available from: https://​www.​google.​co.​uk/​url?​sa=​t&​rct=​j&​q=​&​esrc=​s&​source=​web&​cd=​3&​ved=​0ahUKEwjV8v2m4rP​VAhVpJcAKHXWCBVg​QFggwMAI&​url=​https%3A%2F%2Fwww.nice.org.uk%2Fguidance%2Fta240%2Fdocuments%2Fcolorectal-cancer-metastatic-panitumumab-terminated-appraisal-appendix-b-ge-proposal-paper-january-20152&usg=AFQjCNFLNQSDzjhnmBQESt9XA7YRfoT9hg. Accessed 20 Feb 2018.
24.
go back to reference Tejpar S, Kohne CH, Ciardiello F, Lenz HJ, Heinemann V, Klinkhardt U, et al. FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur J Cancer. 2015;51(10):1243–52.CrossRefPubMed Tejpar S, Kohne CH, Ciardiello F, Lenz HJ, Heinemann V, Klinkhardt U, et al. FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur J Cancer. 2015;51(10):1243–52.CrossRefPubMed
26.
go back to reference England NHS. Cancer drugs fund decision summary: bevacizumab in combination with 1st line single agent fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. London: NHS England; 2015. England NHS. Cancer drugs fund decision summary: bevacizumab in combination with 1st line single agent fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. London: NHS England; 2015.
28.
go back to reference Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. Sheffield: National Institute for Health and Care Excellence Decision Support Unit; 2014. Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. Sheffield: National Institute for Health and Care Excellence Decision Support Unit; 2014.
30.
go back to reference Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–34.CrossRefPubMed Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–34.CrossRefPubMed
32.
go back to reference Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240(4):644–57 (discussion 57–8).PubMedPubMedCentral Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240(4):644–57 (discussion 57–8).PubMedPubMedCentral
37.
go back to reference Latimer NR, Abrams KR, Lambert PC, Crowther MJ, Wailoo AJ, Morden JP, et al. Adjusting survival time estimates to account for treatment switching in randomized controlled trials: an economic evaluation context: methods, limitations, and recommendations. Med Decis Making. 2014;34(3):387–402. https://doi.org/10.1177/0272989X13520192.CrossRefPubMed Latimer NR, Abrams KR, Lambert PC, Crowther MJ, Wailoo AJ, Morden JP, et al. Adjusting survival time estimates to account for treatment switching in randomized controlled trials: an economic evaluation context: methods, limitations, and recommendations. Med Decis Making. 2014;34(3):387–402. https://​doi.​org/​10.​1177/​0272989X13520192​.CrossRefPubMed
38.
go back to reference Curtis L. Unit costs of health and social care 2014. Canterbury: Personal Social Services Research Unit, University of Kent; 2014. Curtis L. Unit costs of health and social care 2014. Canterbury: Personal Social Services Research Unit, University of Kent; 2014.
40.
go back to reference Hoyle M, Crathorne L, Peters J, Jones-Hughes T, Cooper C, Napier M, et al. The clinical effectiveness and cost-effectiveness of cetuximab (mono- or combination chemotherapy), bevacizumab (combination with non-oxaliplatin chemotherapy) and panitumumab (monotherapy) for the treatment of metastatic colorectal cancer after first-line chemotherapy (review of technology appraisal no. 150 and part review of technology appraisal no. 118): a systematic review and economic model. Health Technol Assess. 2013;17(14):1–237. https://doi.org/10.3310/hta17140.CrossRefPubMedPubMedCentral Hoyle M, Crathorne L, Peters J, Jones-Hughes T, Cooper C, Napier M, et al. The clinical effectiveness and cost-effectiveness of cetuximab (mono- or combination chemotherapy), bevacizumab (combination with non-oxaliplatin chemotherapy) and panitumumab (monotherapy) for the treatment of metastatic colorectal cancer after first-line chemotherapy (review of technology appraisal no. 150 and part review of technology appraisal no. 118): a systematic review and economic model. Health Technol Assess. 2013;17(14):1–237. https://​doi.​org/​10.​3310/​hta17140.CrossRefPubMedPubMedCentral
42.
go back to reference Joint Formulary Committee. British national formulary. 69th ed. London: BMJ Group and Pharmaceutical Press; 2015. Joint Formulary Committee. British national formulary. 69th ed. London: BMJ Group and Pharmaceutical Press; 2015.
44.
go back to reference Papaioannou D, Brazier JE, Paisley S. NICE DSU technical support document 9: the identification, review and synthesis of health state utility values from the literature. London: National Institute for Health and Care Excellence; 2010. Papaioannou D, Brazier JE, Paisley S. NICE DSU technical support document 9: the identification, review and synthesis of health state utility values from the literature. London: National Institute for Health and Care Excellence; 2010.
47.
go back to reference Freeman K, Connock M, Cummins E, Gurung T, Taylor-Phillips S, Court R, et al. Fluorouracil plasma monitoring: the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Coventry: Warwick Evidence; 2014. Freeman K, Connock M, Cummins E, Gurung T, Taylor-Phillips S, Court R, et al. Fluorouracil plasma monitoring: the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Coventry: Warwick Evidence; 2014.
48.
go back to reference Huxley N, Crathorne L, Varley-Campbell J, Tikhonova I, Snowsill T, Briscoe S, et al. The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation. Health Technol Assess. 2017;21(38):1–294. https://doi.org/10.3310/hta21380.CrossRefPubMedPubMedCentral Huxley N, Crathorne L, Varley-Campbell J, Tikhonova I, Snowsill T, Briscoe S, et al. The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation. Health Technol Assess. 2017;21(38):1–294. https://​doi.​org/​10.​3310/​hta21380.CrossRefPubMedPubMedCentral
Metadata
Title
Economic Analysis of First-Line Treatment with Cetuximab or Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer in England
Authors
Irina A. Tikhonova
Nicola Huxley
Tristan Snowsill
Louise Crathorne
Jo Varley-Campbell
Mark Napier
Martin Hoyle
Publication date
01-07-2018
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 7/2018
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.1007/s40273-018-0630-9

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