The National Institute of Health and Clinical Excellence (NICE), the UK authority that is charged with determining which treatments should be authorised for use in the National Health Service, has now issued full guidance on the use of three drugs, cetuximab, bevacizumab and panitumumab, in patients with metastatic, progressive colorectal cancer.

This guidance [1], which updates and replaces interim guidance published in 2007 and 2008, is to reject the use of any of these drugs for this indication in the NHS. Fiona Rinaldi, Elisabeth George and Amanda Adler from NICE, based in London, UK, have written an article in the Lancet [2] explaining the reasoning behind this decision and its implications for NHS treatment of advanced colorectal cancer.

These three drugs are all monoclonal antibodies against kinases that have been implicated in cancer development.

Cetuximab and panitumumab are both directed against the epidermal growth factor receptor (EGFR), whereas bevacizumab blocks vascular endothelial growth factor A (VEGF-A), which stimulates angiogenesis.

The evidence for the efficacy of each drug presented by its developer, and the clinical and cost-effectiveness of each treatment, were all assessed for NICE by the independent Peninsula Technology Assessment Group (University of Exeter, Exeter, UK).

All evidence of efficacy presented to the assessors was derived from randomized controlled clinical trials. In the case of bevacizumab, this evidence was derived from the E3200 trial of the drug combined with oxaliplatin chemotherapy and observational studies, and the assessors agreed that the results from the trial did not prove that bevacizumab offered any significant overall survival gain.

Evidence for the efficacy of cetuximab was derived from results of the CO.17 trial in a subset of patients without mutations in the KRAS gene. The results of this trial did indicate that cetuximab plus best supportive care provided a significant increase in progression free survival in this patient group over best supportive care alone.


The assessors concluded, however, that there was a high degree of uncertainty in these results. A randomised controlled trial of panitumumab in a similar patient population showed that giving this drug with best supportive care seemed to offer a progression free survival benefit of about five weeks compared to best supportive care alone, but the assessors concluded that the precise benefit conferred by the drug was still uncertain.

The assessors evaluated the economic costs and benefits of the drugs using a model that compared each drug combined with best supportive care against best supportive care alone; the cetuximab model included combination therapy with irinotecan in the assessment. All economic models were run for ten years and evaluated the incremental cost-effectiveness ratio (ICER) of each drug, including the cetuximab / irinotecan combination, per quality-adjusted life year (QALY) gained.

Although all drugs and combinations were shown to extend life, the estimated ICERs generated ranged from £55,000 for cetuximab with irinotecan to between £110,000 and £150,000 for monotherapy with panitumumab.

The evaluators concluded that none of the drugs appraised could be considered the most cost-effective treatment for progressive, metastatic colorectal cancer. Furthermore, they found none that met the additional criteria used by NICE to appraise drugs that might be of particular value in extending the life expectancy of patients with terminal disease. No appeals were received by the committee and the final guidance rejecting the drugs was published on 25 January 2012.

Reference

[1] NICE. Technology appraisal guidance TA242. Cetuximab, bevacizumab and panitumumab for the treatment of metastatic colorectal cancer after first-line chemotherapy. http://guidance.nice.org.uk/TA/Published

[2] Rinaldi, F., George, E. and Adler, A.I. (2012). NICE guidance on cetuximab, bevacizumab, and panitumumab for treatment of metastatic colorectal cancer after first-line chemotherapy. The Lancet, published online ahead of print 25 January 2012. doi: 10.1016/S1470-2045(12)70044-X