Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer

Abstract

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.

Bevacizumab

“…In a number of European countries, the estimated cost per life-year gained in the treatment of metastatic CRC with bevacizumab is about €80,000. The combination of bevacizumab with irinotecan, 5-fluorouracil, and leucovorin (the IFL regimen) was considered a non-cost-effective treatment by the English National Institute for Health and Clinical Excellence [46,47].…”

Cost‐effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany

“…28 Second, we have not incorporated any quality-of-life adjustments in the model because of the lack of data on utilities for patients with mCRC receiving chemotherapy. 15,29 Third, we have conservatively excluded the cost of supportive therapy such as dermatologic care due to limited data. Any additional cost-savings associated with reduced supportive treatment for KRAS mutant patients will improve the costeffectiveness of KRAS testing.…”

“…4,10,11 Current U.S. and European guidelines recommend that all mCRC patients receive tumor KRAS testing before consideration of treatment with an EGFR inhibitor and state that patients with known KRAS mutations should not receive either cetuximab or panitumumab as there is very little chance of a clinical benefit and the exposure to toxicity and highcost of treatment cannot be justified. 1,2 Although some studies have examined the cost-effectiveness of cetuximab treatment, [12][13][14][15] limited data exist on the cost-effectiveness or the potential cost savings that might accrue from the use of KRAS testing. Our objective was to determine the cost-effectiveness of testing for KRAS mutations before administering cetuximab or panitumumab for patients with mCRC in the United States and Germany and to document the economic implications of KRAS testing.…”

The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation

“…Palliative care costs in the model are estimated at £600 per month and are based on those adopted by Tappenden and colleagues, 160 derived from Remak and Brazil. 163 These costs are applied for the remaining life expectancy of patients who experience disease progression, irrespective of their initial treatment.…”

“…The reduction in quality of life resulting from surgical resection is applied for 6 months, based on profiles reported by Wiering and colleagues 151 and Krabbe and colleagues, 146 while the quality-of-life reduction resulting from ablation is applied for 3 months, based on profiles reported by Krabbe and colleagues. 146 A relative weighting of 0.75 for disease progression is applied in the model, based on an estimate reported by Tappenden and colleagues, 160 derived from Petrou and Campbell 161 which was identified in a systematic review of studies reporting utility values for health states relevant for patients with metastatic colorectal cancer (not specific to people with liver metastases).…”