title: 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.
authors.affiliation: HealthPartners Research Foundation, 8170 33rd Ave. S., Mail Stop 21111R, Bloomington, MN 55425, USA. Ajay.S.Behl@HealthPartners.com
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Behl
authors.forename: Katrina A B
authors.initials: KA
authors.lastname: Goddard
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Flottemesch
authors.forename: David
authors.initials: D
authors.lastname: Veenstra
authors.forename: Richard T
authors.initials: RT
authors.lastname: Meenan
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lin
authors.forename: Michael V
authors.initials: MV
authors.lastname: Maciosek
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000191:economics* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015986:Confounding Factors, Epidemiologic; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005820:Genetic Testing / Q000191:economics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D019057:Quality-Adjusted Life Years; D012107:Research Design; D014481:United States; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins