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
BACKGROUND: Colorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Targeted agents are available, including the antiepidermal growth factor receptor (EGFR) agents cetuximab (Erbitux((R)), Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix((R)), Amgen UK Ltd, Cambridge, UK). OBJECTIVE: To investigate the clinical effectiveness and cost-effectiveness of panitumumab in combination with chemotherapy and cetuximab in combination with chemotherapy for rat sarcoma (RAS) wild-type (WT) patients for the first-line treatment of metastatic colorectal cancer. DATA SOURCES: The assessment included a systematic review of clinical effectiveness and cost-effectiveness studies, a review and critique of manufacturer submissions, and a de novo cohort-based economic analysis. For the assessment of effectiveness, a literature search was conducted up to 27 April 2015 in a range of electronic databases, including MEDLINE, EMBASE and The Cochrane Library. REVIEW METHODS: Studies were included if they were randomised controlled trials (RCTs) or systematic reviews of RCTs of cetuximab or panitumumab in participants with previously untreated metastatic colorectal cancer with RAS WT status. All steps in the review were performed by one reviewer and checked independently by a second. Narrative synthesis and network meta-analyses (NMAs) were conducted for outcomes of interest. An economic model was developed focusing on first-line treatment and using a 30-year time horizon to capture costs and benefits. Costs and benefits were discounted at 3.5% per annum. Scenario analyses and probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS: The searches identified 2811 titles and abstracts, of which five clinical trials were included. Additional data from these trials were provided by the manufacturers. No data were available for panitumumab plus irinotecan-based chemotherapy (folinic acid + 5-fluorouracil + irinotecan) (FOLFIRI) in previously untreated patients. Studies reported results for RAS WT subgroups. First-line treatment with anti-EGFR therapies in combination with chemotherapy appeared to have statistically significant benefits for patients who are RAS WT. For the independent economic evaluation, the base-case incremental cost-effectiveness ratio (ICER) for RAS WT patients for cetuximab plus oxaliplatin-based chemotherapy (folinic acid + 5-fluorouracil + oxaliplatin) (FOLFOX) compared with FOLFOX was £104,205 per quality-adjusted life-year (QALY) gained; for panitumumab plus FOLFOX compared with FOLFOX was £204,103 per QALY gained; and for cetuximab plus FOLFIRI compared with FOLFIRI was £122,554 per QALY gained. The ICERs were sensitive to treatment duration, progression-free survival, overall survival (resected patients only) and resection rates. LIMITATIONS: The trials included RAS WT populations only as subgroups. No evidence was available for panitumumab plus FOLFIRI. Two networks were used for the NMA and model, based on the different chemotherapies (FOLFOX and FOLFIRI), as insufficient evidence was available to the assessment group to connect these networks. CONCLUSIONS: Although cetuximab and panitumumab in combination with chemotherapy appear to be clinically beneficial for RAS WT patients compared with chemotherapy alone, they are likely to represent poor value for money when judged by cost-effectiveness criteria currently used in the UK. It would be useful to conduct a RCT in patients with RAS WT. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015016111. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Citation
@article{n.2017,
author = {Huxley, N. and Crathorne, L. and Varley-Campbell, J. and
Tikhonova, I. and Snowsill, T. and Briscoe, S. and Peters, J. and
Bond, M. and Napier, M. and Hoyle, M.},
title = {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},
journal = {Health Technology Assessment},
volume = {21},
number = {38},
date = {2017-07-01},
url = {https://tristansnowsill.co.uk/the-clinical-effectiveness-and-cost-effectiveness-of.html},
doi = {10.3310/hta21380},
langid = {en},
abstract = {BACKGROUND: Colorectal cancer is the fourth most commonly
diagnosed cancer in the UK after breast, lung and prostate cancer.
People with metastatic disease who are sufficiently fit are usually
treated with active chemotherapy as first- or second-line therapy.
Targeted agents are available, including the antiepidermal growth
factor receptor (EGFR) agents cetuximab (Erbitux((R)), Merck Serono
UK Ltd, Feltham, UK) and panitumumab (Vecitibix((R)), Amgen UK Ltd,
Cambridge, UK). OBJECTIVE: To investigate the clinical effectiveness
and cost-effectiveness of panitumumab in combination with
chemotherapy and cetuximab in combination with chemotherapy for rat
sarcoma (RAS) wild-type (WT) patients for the first-line treatment
of metastatic colorectal cancer. DATA SOURCES: The assessment
included a systematic review of clinical effectiveness and
cost-effectiveness studies, a review and critique of manufacturer
submissions, and a de novo cohort-based economic analysis. For the
assessment of effectiveness, a literature search was conducted up to
27 April 2015 in a range of electronic databases, including MEDLINE,
EMBASE and The Cochrane Library. REVIEW METHODS: Studies were
included if they were randomised controlled trials (RCTs) or
systematic reviews of RCTs of cetuximab or panitumumab in
participants with previously untreated metastatic colorectal cancer
with RAS WT status. All steps in the review were performed by one
reviewer and checked independently by a second. Narrative synthesis
and network meta-analyses (NMAs) were conducted for outcomes of
interest. An economic model was developed focusing on first-line
treatment and using a 30-year time horizon to capture costs and
benefits. Costs and benefits were discounted at 3.5\% per annum.
Scenario analyses and probabilistic and univariate deterministic
sensitivity analyses were performed. RESULTS: The searches
identified 2811 titles and abstracts, of which five clinical trials
were included. Additional data from these trials were provided by
the manufacturers. No data were available for panitumumab plus
irinotecan-based chemotherapy (folinic acid + 5-fluorouracil +
irinotecan) (FOLFIRI) in previously untreated patients. Studies
reported results for RAS WT subgroups. First-line treatment with
anti-EGFR therapies in combination with chemotherapy appeared to
have statistically significant benefits for patients who are RAS WT.
For the independent economic evaluation, the base-case incremental
cost-effectiveness ratio (ICER) for RAS WT patients for cetuximab
plus oxaliplatin-based chemotherapy (folinic acid + 5-fluorouracil +
oxaliplatin) (FOLFOX) compared with FOLFOX was £104,205 per
quality-adjusted life-year (QALY) gained; for panitumumab plus
FOLFOX compared with FOLFOX was £204,103 per QALY gained; and for
cetuximab plus FOLFIRI compared with FOLFIRI was £122,554 per QALY
gained. The ICERs were sensitive to treatment duration,
progression-free survival, overall survival (resected patients only)
and resection rates. LIMITATIONS: The trials included RAS WT
populations only as subgroups. No evidence was available for
panitumumab plus FOLFIRI. Two networks were used for the NMA and
model, based on the different chemotherapies (FOLFOX and FOLFIRI),
as insufficient evidence was available to the assessment group to
connect these networks. CONCLUSIONS: Although cetuximab and
panitumumab in combination with chemotherapy appear to be clinically
beneficial for RAS WT patients compared with chemotherapy alone,
they are likely to represent poor value for money when judged by
cost-effectiveness criteria currently used in the UK. It would be
useful to conduct a RCT in patients with RAS WT. STUDY REGISTRATION:
This study is registered as PROSPERO CRD42015016111. FUNDING: The
National Institute for Health Research Health Technology Assessment
programme.}
}