Cost-effectiveness analysis of screening for KRAS and BRAF mutations in metastatic colorectal cancer

Abstract

Background: In 2009, the American Society of Clinical Oncology recommended that patients with metastatic colorectal cancer (mCRC) who are candidates for anti-epidermal growth factor receptor (EGFR) therapy have their tumors tested for KRAS mutations because tumors with such mutations do not respond to anti-EGFR therapy. Limiting anti-EGFR therapy to those without KRAS mutations will reserve treatment for those likely to benefit while avoiding unnecessary costs and harm to those who would not. Similarly, tumors with BRAF genetic mutations may not respond to anti-EGFR therapy, though this is less clear. Economic analyses of mutation testing have not fully explored the roles of alternative therapies and resection of metastases.

Methods: This paper is based on a decision analytic framework that forms the basis of a cost-effectiveness analysis of screening for KRAS and BRAF mutations in mCRC in the context of treatment with cetuximab. A cohort of 50 000 patients with mCRC is simulated 10 000 times, with attributes randomly assigned on the basis of distributions from randomized controlled trials.

Results: Screening for both KRAS and BRAF mutations compared with the base strategy (of no anti-EGFR therapy) increases expected overall survival by 0.034 years at a cost of $22 033, yielding an incremental cost-effectiveness ratio of approximately $650 000 per additional year of life. Compared with anti-EGFR therapy without screening, adding KRAS testing saves approximately $7500 per patient; adding BRAF testing saves another $1023, with little reduction in expected survival.

Conclusions: Screening for KRAS and BFAF mutation improves the cost-effectiveness of anti-EGFR therapy, but the incremental cost effectiveness ratio remains above the generally accepted threshold for acceptable cost effectiveness ratio of $100 000/quality adjusted life year.

Figure 1.

Markov model of disease progression and treatment in metastatic colorectal cancer. Clone 1, Clone 2 are clone copies of the master clone subtrees 1 and 2, indicated by the respectively numbered heavy lines. The clone copies have the same structure as but can have different calculations from the master clone subtrees. Legend: : Terminal node (the outcome because of following a path); : Logical node (logical decisions are made based on logical structure in the node); : Markov node (indicates the presence of a hidden or shown Markov subtree at the node); : Decision node (indicates the point of decision, which in our case is choosing between the four strategies); KRAS = V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, BRAF = serine/threonine-protein kinase B-Raf, EGFR = epidermal growth factor receptor, VEGF = vascular endothelial growth factor.

Figure 2.

Cost-effectiveness analysis of four strategies with no anti-EGFR therapy as the base strategy.

Figure 3.

Costs and effectiveness scatter plot.

Figure 4.

Cost-effectiveness acceptability curves of anti-EGFR therapies. WTP: Willingness to pay, LYS = Life year saved, KRAS = V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, BRAF = serine/threonine-protein kinase B-Raf, EGFR = epidermal growth factor receptor.

Figure 5.

Acceptability frontier. WTP = Willingness to pay, LYS = Life year saved, KRAS = V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, BRAF = serine/threonine-protein kinase B-Raf, EGFR = epidermal growth factor receptor.