title: Cost-effectiveness analysis of KRAS testing and cetuximab as last-line therapy for colorectal cancer.
abstract: BACKGROUND
  Cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves progression-free survival and overall survival in patients with metastatic colorectal cancer (mCRC). However, patients with a KRAS gene mutation do not benefit from cetuximab therapy.
  
  
  METHODS
  We performed a cost-effectiveness analysis of KRAS testing and cetuximab treatment as last-line therapy for patients with mCRC in Japan. In our analysis, we considered three treatment strategies. In the 'KRAS-testing strategy' (strategy A), KRAS testing was performed to guide treatment: patients with wild-type KRAS received cetuximab, and those with mutant KRAS received best supportive care (BSC). In the 'no-KRAS-testing strategy' (strategy B), genetic testing was not conducted and all patients received cetuximab. In the 'no-cetuximab strategy' (strategy C), genetic testing was not conducted and all patients received BSC. To evaluate the cost effectiveness of KRAS testing, the KRAS-testing strategy was compared with the no-KRAS-testing strategy; to evaluate the cost effectiveness of KRAS testing and cetuximab, the KRAS-testing strategy was compared with the no-cetuximab strategy; and to evaluate the cost effectiveness of cetuximab treatment without KRAS testing, the no-KRAS-testing strategy was compared with the no-cetuximab strategy. A three-state Markov model was used to predict expected costs and outcomes for each group. Outcomes in the model were based on those reported in a retrospective analysis of data from the National Cancer Institute of Canada Clinical Trials Group CO.17 study. We included only direct medical costs from the perspective of the Japanese healthcare payer. A 3% discount rate was used for both costs and outcome. Two outcomes, life-years (LYs) gained and quality-adjusted life-years (QALYs) gained, were used to calculate the incremental cost-effectiveness ratio (ICER).
  
  
  RESULTS
  Our cost-effectiveness analysis revealed that the KRAS-testing strategy was dominant compared with the no-KRAS-testing strategy, with an expected cost reduction of ¥0.5 million per patient and an estimated budget impact of ¥3-5 billion ($US42-59 million; July 2010 values) per year. The ICER of the KRAS-testing strategy compared with the no-cetuximab strategy was ¥11 million ($US120 000) per LY gained and ¥16 million ($US160 000) per QALY gained, whereas the ICER of the KRAS-testing strategy compared with the no-KRAS-testing strategy was ¥14 million ($US180 000) per LY gained and ¥21 million ($US230 000) per QALY gained. These results were supported by the sensitivity analysis.
  
  
  CONCLUSIONS
  KRAS testing is recommended before administering cetuximab as last-line therapy for patients with mCRC. However, our analysis suggests that the ICER of cetuximab treatment (with or without KRAS testing) is too high, even if treatment is limited to patients with wild-type KRAS.
authors.affiliation: Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. t.shiroiwa@gmail.com
authors.forename: Takeru
authors.initials: T
authors.lastname: Shiroiwa
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Motoo
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Tsutani
mesh_terms: D000911:Antibodies, Monoclonal / Q000191:economics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000191:economics; D003362:Cost-Benefit Analysis; D005820:Genetic Testing / Q000191:economics*; D006801:Humans; D007564:Japan; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016019:Survival Analysis; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab