Abstract

Evidence from a retrospective analysis of multiple large phase iii trials suggested that primary tumour location (ptl) in RAS wild-type metastatic colorectal cancer (wtRAS mcrc) might have predictive value with respect to response to drug therapies. Recent studies also show a potential preferential benefit for epidermal growth factor inhibitors (egfris) for left-sided tumours. In the present study, we aimed to determine the incremental cost-effectiveness ratio (icer) for the first-line use of an egfri for patients with left-sided wtRAS mcrc. We developed a state-transition model to determine the cost effectiveness of alternative treatment strategies in patients with left-sided mcrc:■ Standard of care■ Use of an egfri in first-line therapyThe cohort for the study consisted of patients diagnosed with unresectable wtRAS mcrc with an indication for chemotherapy and previously documented ptl. Model parameters were obtained from the published literature and calibration. The perspective was that of a provincial ministry of health in Canada. We used a 5-year time horizon and an annual discount rate of 1.5%. Selecting patients for first-line egfri treatment based on left-sided location of their colorectal primary tumour was more effective than the standard of care, resulting in an increase in quality-adjusted life-years (qalys) of 0.226 (or 0.644 life-years gained). However, the strategy was also more expensive, costing an average of $60,639 more per patient treated. The resulting icer was $268,094 per qaly. A 35% price reduction in the cost of egfri would be needed to make this strategy cost-effective at a willingness-to-pay threshold (wtp) of $100,000 per qaly. Selective use of an egfri based on ptl was more cost-effective than unselected use of those agents; however, based on traditional wtp thresholds, it was still not cost-effective. While awaiting the elucidation of more precise predictive biomarkers that might improve cost-effectiveness, the price of egfris could be reduced to meet the wtp threshold.

Highlights

  • Evidence from a retrospective analysis of multiple large phase iii trials suggested that primary tumour location in RAS wild-type metastatic colorectal cancer might have predictive value with respect to response to drug therapies

  • Selective use of an egfri based on ptl was more cost-effective than unselected use of those agents; based on traditional wtp thresholds, it was still not cost-effective

  • The results indicated that patients with left-sided ptl experience a significantly greater os benefit from the first-line use of regimens containing egfris compared with the first-line use of regimens containing the vegf inhibitor bevacizumab[7]

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Summary

Introduction

Evidence from a retrospective analysis of multiple large phase iii trials suggested that primary tumour location (ptl) in RAS wild-type metastatic colorectal cancer (wtRAS mcrc) might have predictive value with respect to response to drug therapies. Two recent systematic reviews and their corresponding meta-analyses based on a retrospective examination of randomized clinical trials confirm the predictive relevance of ptl when using targeted therapies for the treatment of patients with left-sided compared with right-sided KRAS wild-type mcrc[7,8]. The results indicated that patients with left-sided ptl experience a significantly greater os benefit from the first-line use of regimens containing egfris (cetuximab or panitumumab) compared with the first-line use of regimens containing the vegf inhibitor bevacizumab (hazard ratio: 0.71; 95% confidence interval: 0.58 to 0.85; p < 0.0003)[7]. In Canada, similar consensus recommendations based on ptl have been made for first-line treatment[10]

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