Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer

Raymond H. Henderson; Declan French; Ethna McFerran; Richard Adams; Harpreet Wasan; Robert Glynne-Jones; David Fisher; Susan Richman; Philip D. Dunne; Lisa Wilde; Timothy S. Maughan; Richard Sullivan; Mark Lawler

doi:10.1016/j.jcpo.2022.100342

Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer

Raymond H. Henderson^*, Declan French, Ethna McFerran, Richard Adams, Harpreet Wasan, Robert Glynne-Jones, David Fisher, Susan Richman, Philip D. Dunne, Lisa Wilde, Timothy S. Maughan, Richard Sullivan, Mark Lawler

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Background: In 2014, the COIN-B clinical trial demonstrated that intermittent cetuximab (IC) was a safe alternative to continuous cetuximab (CC), with less cytotoxic chemotherapy, in first-line treatment for KRAS wild-type metastatic colorectal cancer (mCRC). Cetuximab has been available for this indication in England since 2015, but treatment breaks beyond 6 weeks were prohibited, despite real-world evidence that therapy de-escalation maintains equivalent disease control, but with superior Quality-of-Life (QoL). We performed health economic analyses of IC versus CC and used this evidence to help underpin policy change and guide clinical practice through reduction in unnecessary treatment for mCRC patients. Methods: Employing cost-minimization analysis, we conducted partitioned survival modelling (PSM) and Markov Chain Monte-Carlo (MCMC) simulation to determine costs and quality-adjusted-life-years for IC versus CC. Results: IC reduced costs by £ 35,763 (PSM; p < 0.001) or £ 30,189 (MCMC) per patient annually, while preserving treatment efficacy and enhancing QoL. Extrapolating to all mCRC patients eligible for cetuximab therapy would have generated cost savings of ~£ 1.2 billion over this cohort's lifetime. These data helped underpin a request to NHS England to remove treatment break restrictions in first-line mCRC therapy, which has been adopted as an interim treatment option policy in colorectal cancer during the Covid-19 pandemic. Conclusions: Our results highlight substantial cost savings achievable by treatment de-escalation, while also reinforcing the importance of therapy breaks to potentially increase tumour responsiveness and reduce treatment toxicity. Our study also highlights how health economic evidence can influence health policy, championing reduced treatment intensity approaches without compromising patient outcomes, which is of particular relevance when addressing the reduced capacity and treatment backlogs experienced during the pandemic.

Original language	English
Article number	100342
Journal	Journal of Cancer Policy
Volume	33
DOIs	https://doi.org/10.1016/j.jcpo.2022.100342
Publication status	Published - Sept 2022

Keywords

Biomarker
Cetuximab
Colorectal cancer
Economic evaluation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jcpo.2022.100342

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Henderson, R. H., French, D., McFerran, E., Adams, R., Wasan, H., Glynne-Jones, R., Fisher, D., Richman, S., Dunne, P. D., Wilde, L., Maughan, T. S., Sullivan, R., & Lawler, M. (2022). Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer. Journal of Cancer Policy, 33, Article 100342. https://doi.org/10.1016/j.jcpo.2022.100342

@article{d478c3ba67334cd1917e7df87197dacf,

title = "Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer",

abstract = "Background: In 2014, the COIN-B clinical trial demonstrated that intermittent cetuximab (IC) was a safe alternative to continuous cetuximab (CC), with less cytotoxic chemotherapy, in first-line treatment for KRAS wild-type metastatic colorectal cancer (mCRC). Cetuximab has been available for this indication in England since 2015, but treatment breaks beyond 6 weeks were prohibited, despite real-world evidence that therapy de-escalation maintains equivalent disease control, but with superior Quality-of-Life (QoL). We performed health economic analyses of IC versus CC and used this evidence to help underpin policy change and guide clinical practice through reduction in unnecessary treatment for mCRC patients. Methods: Employing cost-minimization analysis, we conducted partitioned survival modelling (PSM) and Markov Chain Monte-Carlo (MCMC) simulation to determine costs and quality-adjusted-life-years for IC versus CC. Results: IC reduced costs by £ 35,763 (PSM; p < 0.001) or £ 30,189 (MCMC) per patient annually, while preserving treatment efficacy and enhancing QoL. Extrapolating to all mCRC patients eligible for cetuximab therapy would have generated cost savings of ~£ 1.2 billion over this cohort's lifetime. These data helped underpin a request to NHS England to remove treatment break restrictions in first-line mCRC therapy, which has been adopted as an interim treatment option policy in colorectal cancer during the Covid-19 pandemic. Conclusions: Our results highlight substantial cost savings achievable by treatment de-escalation, while also reinforcing the importance of therapy breaks to potentially increase tumour responsiveness and reduce treatment toxicity. Our study also highlights how health economic evidence can influence health policy, championing reduced treatment intensity approaches without compromising patient outcomes, which is of particular relevance when addressing the reduced capacity and treatment backlogs experienced during the pandemic.",

keywords = "Biomarker, Cetuximab, Colorectal cancer, Economic evaluation",

author = "Henderson, {Raymond H.} and Declan French and Ethna McFerran and Richard Adams and Harpreet Wasan and Robert Glynne-Jones and David Fisher and Susan Richman and Dunne, {Philip D.} and Lisa Wilde and Maughan, {Timothy S.} and Richard Sullivan and Mark Lawler",

note = "Funding Information: COIN-B (ISRCTN38375681) was designed by the COIN TMG. It was approved by the South West Research Ethics Committees and the Medicines and Healthcare Regulatory Agency (MHRA) in the UK and the National Bioethics Committee and the Pharmaceutical Services of the Ministry of Health in Cyprus. The MRC was the sponsor. The trial was conducted by the MRC Clinical Trials Unit (CTU) overseen by an Independent Trial Steering Committee following the principles of Good Clinical Research Practice. Data collection at UK sites was supported by the National Cancer Research Networks. Funding Information: The stratification in colorectal cancer consortium (S:CORT) (T.M, M.L.) is co-funded by Cancer Research UK and the UK Medical Research Council (MRC) Stratified Medicine Consortium programme grant (grant ref MR/M016587/1). Cancer Focus Northern Ireland (E.M.F.), Health Data Research UK (E.M.F.), Yorkshire Cancer Research, UKRI GCRF (ES/P010962/1.). Cetuximab drug and support for the trial was provided by Merck. Discounted products were provided by Wyeth and Baxter. Funding Information: The stratification in colorectal cancer consortium (S:CORT) (T.M, M.L.) is co-funded by Cancer Research UK and the UK Medical Research Council (MRC) Stratified Medicine Consortium programme grant (grant ref MR/M016587/1 ). Cancer Focus Northern Ireland (E.M.F.), Health Data Research UK (E.M.F.), Yorkshire Cancer Research , UKRI GCRF ( ES/P010962/1 .). Cetuximab drug and support for the trial was provided by Merck. Discounted products were provided by Wyeth and Baxter. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = sep,

doi = "10.1016/j.jcpo.2022.100342",

language = "English",

volume = "33",

journal = "Journal of Cancer Policy",

issn = "2213-5383",

publisher = "Elsevier BV",

}

Henderson, RH, French, D, McFerran, E, Adams, R, Wasan, H, Glynne-Jones, R, Fisher, D, Richman, S, Dunne, PD, Wilde, L, Maughan, TS, Sullivan, R & Lawler, M 2022, 'Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer', Journal of Cancer Policy, vol. 33, 100342. https://doi.org/10.1016/j.jcpo.2022.100342

TY - JOUR

T1 - Spend less to achieve more

T2 - Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer

AU - Henderson, Raymond H.

AU - French, Declan

AU - McFerran, Ethna

AU - Adams, Richard

AU - Wasan, Harpreet

AU - Glynne-Jones, Robert

AU - Fisher, David

AU - Richman, Susan

AU - Dunne, Philip D.

AU - Wilde, Lisa

AU - Maughan, Timothy S.

AU - Sullivan, Richard

AU - Lawler, Mark

N1 - Funding Information: COIN-B (ISRCTN38375681) was designed by the COIN TMG. It was approved by the South West Research Ethics Committees and the Medicines and Healthcare Regulatory Agency (MHRA) in the UK and the National Bioethics Committee and the Pharmaceutical Services of the Ministry of Health in Cyprus. The MRC was the sponsor. The trial was conducted by the MRC Clinical Trials Unit (CTU) overseen by an Independent Trial Steering Committee following the principles of Good Clinical Research Practice. Data collection at UK sites was supported by the National Cancer Research Networks. Funding Information: The stratification in colorectal cancer consortium (S:CORT) (T.M, M.L.) is co-funded by Cancer Research UK and the UK Medical Research Council (MRC) Stratified Medicine Consortium programme grant (grant ref MR/M016587/1). Cancer Focus Northern Ireland (E.M.F.), Health Data Research UK (E.M.F.), Yorkshire Cancer Research, UKRI GCRF (ES/P010962/1.). Cetuximab drug and support for the trial was provided by Merck. Discounted products were provided by Wyeth and Baxter. Funding Information: The stratification in colorectal cancer consortium (S:CORT) (T.M, M.L.) is co-funded by Cancer Research UK and the UK Medical Research Council (MRC) Stratified Medicine Consortium programme grant (grant ref MR/M016587/1 ). Cancer Focus Northern Ireland (E.M.F.), Health Data Research UK (E.M.F.), Yorkshire Cancer Research , UKRI GCRF ( ES/P010962/1 .). Cetuximab drug and support for the trial was provided by Merck. Discounted products were provided by Wyeth and Baxter. Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022/9

Y1 - 2022/9

N2 - Background: In 2014, the COIN-B clinical trial demonstrated that intermittent cetuximab (IC) was a safe alternative to continuous cetuximab (CC), with less cytotoxic chemotherapy, in first-line treatment for KRAS wild-type metastatic colorectal cancer (mCRC). Cetuximab has been available for this indication in England since 2015, but treatment breaks beyond 6 weeks were prohibited, despite real-world evidence that therapy de-escalation maintains equivalent disease control, but with superior Quality-of-Life (QoL). We performed health economic analyses of IC versus CC and used this evidence to help underpin policy change and guide clinical practice through reduction in unnecessary treatment for mCRC patients. Methods: Employing cost-minimization analysis, we conducted partitioned survival modelling (PSM) and Markov Chain Monte-Carlo (MCMC) simulation to determine costs and quality-adjusted-life-years for IC versus CC. Results: IC reduced costs by £ 35,763 (PSM; p < 0.001) or £ 30,189 (MCMC) per patient annually, while preserving treatment efficacy and enhancing QoL. Extrapolating to all mCRC patients eligible for cetuximab therapy would have generated cost savings of ~£ 1.2 billion over this cohort's lifetime. These data helped underpin a request to NHS England to remove treatment break restrictions in first-line mCRC therapy, which has been adopted as an interim treatment option policy in colorectal cancer during the Covid-19 pandemic. Conclusions: Our results highlight substantial cost savings achievable by treatment de-escalation, while also reinforcing the importance of therapy breaks to potentially increase tumour responsiveness and reduce treatment toxicity. Our study also highlights how health economic evidence can influence health policy, championing reduced treatment intensity approaches without compromising patient outcomes, which is of particular relevance when addressing the reduced capacity and treatment backlogs experienced during the pandemic.

AB - Background: In 2014, the COIN-B clinical trial demonstrated that intermittent cetuximab (IC) was a safe alternative to continuous cetuximab (CC), with less cytotoxic chemotherapy, in first-line treatment for KRAS wild-type metastatic colorectal cancer (mCRC). Cetuximab has been available for this indication in England since 2015, but treatment breaks beyond 6 weeks were prohibited, despite real-world evidence that therapy de-escalation maintains equivalent disease control, but with superior Quality-of-Life (QoL). We performed health economic analyses of IC versus CC and used this evidence to help underpin policy change and guide clinical practice through reduction in unnecessary treatment for mCRC patients. Methods: Employing cost-minimization analysis, we conducted partitioned survival modelling (PSM) and Markov Chain Monte-Carlo (MCMC) simulation to determine costs and quality-adjusted-life-years for IC versus CC. Results: IC reduced costs by £ 35,763 (PSM; p < 0.001) or £ 30,189 (MCMC) per patient annually, while preserving treatment efficacy and enhancing QoL. Extrapolating to all mCRC patients eligible for cetuximab therapy would have generated cost savings of ~£ 1.2 billion over this cohort's lifetime. These data helped underpin a request to NHS England to remove treatment break restrictions in first-line mCRC therapy, which has been adopted as an interim treatment option policy in colorectal cancer during the Covid-19 pandemic. Conclusions: Our results highlight substantial cost savings achievable by treatment de-escalation, while also reinforcing the importance of therapy breaks to potentially increase tumour responsiveness and reduce treatment toxicity. Our study also highlights how health economic evidence can influence health policy, championing reduced treatment intensity approaches without compromising patient outcomes, which is of particular relevance when addressing the reduced capacity and treatment backlogs experienced during the pandemic.

KW - Biomarker

KW - Cetuximab

KW - Colorectal cancer

KW - Economic evaluation

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U2 - 10.1016/j.jcpo.2022.100342

DO - 10.1016/j.jcpo.2022.100342

M3 - Article

C2 - 35718327

AN - SCOPUS:85133329515

SN - 2213-5383

VL - 33

JO - Journal of Cancer Policy

JF - Journal of Cancer Policy

M1 - 100342

ER -

Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer

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UN SDGs

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