Cost-Effectiveness of Targeted Therapy With Cetuximab in Patients With K-ras Wild-Type Colorectal Cancer Presenting With Initially Unresectable Metastases Limited to the Liver in a German Setting

Background: In patients with metastases limited to the liver (liver-limited disease [LLD]) effective therapies such as monoclonal antibodies combined with chemotherapy may facilitate metastasis resection and improve long-term survival. Objective: This study assessed the cost-effectiveness of bevacizumab and cetuximab in the treatment of patients with colorectal cancer presenting with initially unresectable liver metastases of the Kirsten rat sarcoma viral oncogene homolog (K-ras) wild type, from the perspective of German statutory health insurance. Methods: The health-economic modeling approach presented here made indirect comparisons between available data on bevacizumab and cetuximab treatment outcomes using evidence synthesis techniques, extrapolating from the follow-up duration of identified clinical trials to a longer time horizon of up to 10 years and inferring costs and health outcomes based on modeled patient pathways. Expert opinion and Delphi panel methods were used for some assumptions, when evidence was missing. Probabilistic sensitivity analyses and different scenario analyses were applied to test for uncertainty around input parameters and assumptions. Results: For the metastatic colorectal cancer LLD population with K-ras wild-type genotype, mean overall survival estimates were 37.7 months for first-line treatment with cetuximab plus FOLFIRI (irinotecan, leucovorin, fluorouracil) and 30.4 months for bevacizumab plus FOLFOX (oxaliplatin, leucovorin, fluorouracil). Corresponding discounted survival estimates were 2.88 life-years with cetuximab plus FOLFIRI versus 2.38 life-years with bevacizumab plus FOLFOX, an average gain of 0.50 discounted life-years. The incremental cost-effectiveness ratio of cetuximab plus FOLFIRI versus bevacizumab plus FOLFOX was 15,020 (year 2010) per life-year gained in the base case (with a 95% CI from the probabilistic sensitivity analysis of 3806 24,660). Results were robust in different scenario analyses as well as in the probabilistic sensitivity analysis. Conclusions: First-line treatment with cetuximab plus FOLFIRI offers a cost-effective treatment option versus bevacizumab plus FOLFOX for the metastatic colorectal cancer LLD population with K-ras wild-type genotype in Germany. K-ras testing should be performed on all presenting cases of metastatic colorectal cancer to ensure access to this treatment option. (Clin Ther. 2011;33:482-497) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.