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The trials indicate that bevacizumab in combination with 5-FU/FA, and bevacizumab in combination with IFL, is clinically effective in comparison to standard chemotherapy options for the first-line treatment of metastatic CRC. The health economic analysis suggests that the marginal cost-utility of bevacizumab plus IFL versus IFL is unlikely to be better than pound 62,857 per QALY gained, and the marginal cost-utility of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 88,658 per QALY gained. There is no direct evidence to demonstrate whether cetuximab in combination with irinotecan improves health-related quality of life or OS in comparison to active/best supportive care or oxaliplatin plus 5-FU/FA, although the evidence on tumour response rates suggests that cetuximab plus irinotecan has some clinical activity. While it is difficult to suggest whether cetuximab represents value for money, indirect comparisons suggest that the incremental cost-utility of cetuximab plus irinotecan is unlikely to be better than pound 30,000 per QALY gained. This review highlights a number of areas for further research, including clarifying the true impact of first-line bevacizumab in combination with irinotecan and/or infusional 5-FU/FA, without subsequent bevacizumab treatment following disease progression, on OS in patients with metastatic CRC who are representative of the typical population of CRC patients in England and Wales. Further research concerning the impact of therapies on health-related quality of life is essential.

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