Cost-effectiveness of RAS testing in colorectal cancer. A systematic review of economic evaluations

Background: Epidermal growth factor receptor (EGFR) inhibitors have shown benefit in the treatment of metastatic colorectal cancer (mCRC), particularly when combined with predictive biomarkers of response. The most important is RAS mutational status: international guidelines recommend to reserve anti-EGFR treatment only to RAS wild-type tumors, as they are likely to benefit from it. We aimed to review the cost-effectiveness of RAS testing in selecting mCRC patients for anti-EGFR treatment. Methods: We performed a systematic review of full economic evaluations comparing testing for RAS mutational status in mCRC patients prior to anti-EGFR treatment with no-testing. We searched Medline, the Health Technology Assessment Database, the National Health Service Economic Evaluation Database, Scopus, and ISI Web of Science for English papers published since 2000. The quality of the included studies was assessed using the Quality of Health Economic Studies scale. Results: We included 7 economic evaluations (2 cost-effectiveness analyses; 3 cost-utility analyses; 2 cost-effectiveness and cost utility analyses) conducted between 2000 and 2017 in various Countries (Switzerland; Germany; USA; Canada; Japan; China). All studies showed good quality and adopted the perspective of the healthcare system/payer, thus only direct medical costs were analyzed. All studies except one presented at least one strategy with a favorable ICER for RAS testing prior to anti-EGFR therapy. Conclusions: Even if testing for RAS mutational status prior to anti-EGFR therapy increases costs, still it is a cost-effective strategy compared to anti-EGFR therapy without testing. Nevertheless, existing economic evaluations showed some limitations that should be addressed with future research, such as the impact of anti-EGFR toxicity and the introduction of comprehensive molecular profiling. The treatment of mCRC is shifting to a more personalized approach which is essential for avoiding unnecessary toxicity and costs.