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

Abstract

BackgroundColorectal 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®, Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix®, Amgen UK Ltd, Cambridge, UK).ObjectiveTo 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 sourcesThe 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 methodsStudies 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 withRASWT 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.ResultsThe 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 forRASWT subgroups. First-line treatment with anti-EGFR therapies in combination with chemotherapy appeared to have statistically significant benefits for patients who areRASWT. For the independent economic evaluation, the base-case incremental cost-effectiveness ratio (ICER) forRASWT 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.LimitationsThe trials includedRASWT 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.ConclusionsAlthough cetuximab and panitumumab in combination with chemotherapy appear to be clinically beneficial forRASWT 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 withRASWT.Study registrationThis study is registered as PROSPERO CRD42015016111.FundingThe National Institute for Health Research Health Technology Assessment programme.

Effectiveness and Costs Associated to Adding Cetuximab or Bevacizumab to Chemotherapy as Initial Treatment in Metastatic Colorectal Cancer: Results from the Observational FABIO Project

“…Finally, as far as the cost-effectiveness profile is concerned, our findings are consistent with recent studies showing that (i) adding bevacizumab to first-line chemotherapy in mCRC patients was not cost-effective in five countries, including the U.S., the U.K., Canada, Australia and Israel [11]; (ii) the cost-effectiveness value of cetuximab in K-RAS wild-type previously untreated mCRC patients is poor in the U.K. [13].…”

Cost-effectiveness of FOLFIRI + cetuximab vs FOLFIRI + bevacizumab in the first-line treatment ofRASwild-type metastatic colorectal cancer in Germany: data from the FIRE-3 (AIO KRK-0306) study

“…ICER estimates for the alternative scenario analysis were not provided in the Huxley et al manuscript. Our results in terms of undiscounted life years align with the Huxley scenario, while residual differences between ICER estimates can be explained by modeling based on KM data (our study) versus parametric survival curves 27 . This narrows the gap between calculated ICERs substantially.…”

“…To our knowledge, our study is the first full report on a model based on patient-level data from the FIRE-3 trial. The clinical efficacy and cost-effectiveness of cetuximab for the first-line treatment of RAS wt mCRC in the United Kingdom were previously assessed by the Peninsula Technology Assessment Group and published by Huxley et al 27 . It should Abbreviations.…”

“…model. Additionally, BSC costs were updated to match Bekelman et al 30 , and end-of-life costs were incorporated into the base case to be in line with previous comparable costeffectiveness models 25,27,31,32 . Since BSC costs cannot always be distinguished from end-of-life costs, the potential to overestimate costs cannot be ruled out, notably in the cetuximab arm, where survival was longer.…”

Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy

“…Therefore, advanced target therapies, such as monoclonal antibodies (bevacizumab) or proteins (aflibercept) against vascular endothelial growth factor, and against the epidermal growth factor receptor (EGFR), respectively, in combination with chemotherapy, should be considered in patients with metastatic CRC (mCRC), since they improve the outcome of mCRC patients . However, the high costs associated with these targeted therapies limit their application in developing countries, including Paraguay …”