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Cost-Effectiveness Analysis of KRAS Testing and Cetuximab as Last-Line Therapy for Colorectal Cancer

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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 wildtype 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 ($US42–59 million; July 2010 values) per year. The ICER of the KRAS- testing strategy compared with the no-cetuximab strategy was ¥11 million ($US120000) 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.

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Acknowledgments

This study was supported by Roche Diagnostics K.K. Our work was not influenced by the funder. There are no other conflicts of interest to report.

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Authors and Affiliations

  1. Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Takeru Shiroiwa & Kiichiro Tsutani

  2. Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Shiga, Japan

    Takeru Shiroiwa

  3. Department of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa, Japan

    Yoshiharu Motoo

Authors
  1. Takeru Shiroiwa
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  2. Yoshiharu Motoo
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  3. Kiichiro Tsutani
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Corresponding author

Correspondence to Takeru Shiroiwa.

Appendix

Appendix

The differences between the patient populations used in our analysis versus those used in the Canadian analysis[29] of the NCIC CO.17 trial[14] data are defined below. See table A-1 for details of study population subgroups (1) to (6).

Table A-1
figure TabA1

Study population subgroups based on KRAS mutation status and treatment

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Population of our Analysis

  • In the KRAS-testing strategy, patients consisted of (1) and (4);

  • in the no-KRAS-testing strategy, patients consisted of (1) and (3); and

  • in the no-cetuximab strategy, patients consisted of (2) and (4).

We compared three strategies with each other: (1) + (4)vs(1) + (3)vs(2) + (4).

Population of Canadian Analysis

  • In the entire study population, the cetuximab group consisted of (1), (3), and (5), and the BSC group consisted of (2), (4), and (6).

  • In the wild-type KRAS population, the cetuximab group was (1) and the BSC group was (2).

The Canadian analysis compared cetuximab with BSC in two populations: (1) + (3) + (5) vs (2)+ (4)+ (6), and (1) vs (2).

  1. 1.

    Patients with wild-type KRAS treated with cetuximab.

  2. 2.

    Patients with wild-type KRAS treated with BSC.

  3. 3.

    Patients with mutant KRAS treated with cetuximab.

  4. 4.

    Patients with mutant KRAS treated with BSC.

  5. 5.

    Patients with unknown KRAS status treated with cetuximab.

  6. 6.

    Patients with unknown KRAS status treated with BSC.

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Shiroiwa, T., Motoo, Y. & Tsutani, K. Cost-Effectiveness Analysis of KRAS Testing and Cetuximab as Last-Line Therapy for Colorectal Cancer. Mol Diag Ther 14, 375–384 (2010). https://doi.org/10.1007/BF03256395

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