Journal of the National Cancer Institute Advance Access originally published online on August 7, 2009
JNCI Journal of the National Cancer Institute 2009 101(17):1182-1192; doi:10.1093/jnci/djp232
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Prospective Cost-Effectiveness Analysis of Cetuximab in Metastatic Colorectal Cancer: Evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 Trial
Affiliations of authors: Health Outcomes and Pharmacoeconomics Research Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada (NM, PKI); Clinical Trials Group, National Cancer Institute of Canada, Kingston, ON, Canada (NM, H-JA, DT, CJO, WKE, BF, DJJ); Australasian Gastrointestinal Trials Group (JRZ, JS, BF, NCT, ML); Department of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada (H-JA); Department of Community Department of Health and Epidemiology, Queen's University, Kingston, ON, Canada (CJO); Department of Medical Oncology, Flinders Medical Centre, Adelaide, Australia (CSK); Division of Haematology & Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia (JRZ); Department of Oncology, McMaster University and Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON, Canada (WKE); Division of Medical Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada (MJM); Department of Medical Oncology, Dr. H. Bliss Murphy Cancer Centre, St. John's, NL, Canada (JS); Division of Oncology, Niagara Health System, St. Catharines, ON, Canada (BF); Division of Medical Oncology, Dalhousie University and Queen Elizabeth Health Sciences Center, Halifax, NS, Canada (BC); National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (JS); Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Australia (PG); Cancer Care, University of New South Wales Clinical School, St George Hospital, Sydney, Australia (ML); Ludwig Oncology Unit, Austin Health, Melbourne, Australia (NCT); Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada (DJJ)
Correspondence to: Nicole Mittmann, Health Outcomes and Pharmacoeconomics Research Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada M4N 3M5; Department of Pharmacology, University of Toronto, 2075 Bayview Ave, E240, Toronto, ON, Canada M4N 3M5 (e-mail: nicole.mittmann{at}sunnybrook.ca).
Background: The National Cancer Institute of Canada Clinical Trials Group CO.17 study showed that patients with advanced colorectal cancer had improved overall survival when cetuximab, an epidermal growth factor receptor–targeting antibody, was given in addition to best supportive care. We conducted a cost-effectiveness analysis using prospectively collected resource utilization and health utility data for patients in the CO.17 study who received cetuximab plus best supportive care (N = 283) or best supportive care alone (N = 274).
Methods: Direct medical resource utilization data were collected, including medications, physician visits, toxicity management, blood products, emergency department visits, and hospitalizations. Mean survival times for the study arms were calculated for the entire population and for the subset of patients with wild-type KRAS tumors over an 18- to 19-month period. All costs were presented in 2007 Canadian dollars. One-way and probabilistic sensitivity analysis was used to determine the robustness of the results. Cost-effectiveness acceptability curves were determined. The 95% confidence intervals (CIs) for the incremental cost-effectiveness ratios and the incremental cost–utility ratios were estimated by use of a nonparametric bootstrapping method (with 1000 iterations).
Results: For the entire study population, the mean improvement in overall and quality-adjusted survival with cetuximab was 0.12 years and 0.08 quality-adjusted life-years (QALYs), respectively. The incremental cost with cetuximab compared with best supportive care was $23 969. The incremental cost-effectiveness ratio was $199 742 per life-year gained (95% CI = $125 973 to $652 492 per life-year gained) and the incremental cost–utility ratio was $299 613 per QALY gained (95% CI = $187 440 to $898 201 per QALY gained). For patients with wild-type KRAS tumors, the incremental cost with cetuximab was $33 617 and mean gains in overall and quality-adjusted survival were 0.28 years and 0.18 QALYs, respectively. The incremental cost-effectiveness ratio was $120 061 per life-year gained (95% CI = $88 679 to $207 075 per life-year gained) and the incremental cost–utility ratio was $186 761 per QALY gained (95% CI = $130 326 to $334 940 per QALY gained). In a sensitivity analysis, cetuximab cost and patient survival were the only variables that influenced cost-effectiveness.
Conclusions: The incremental cost-effectiveness ratio of cetuximab over best supportive care alone in unselected advanced colorectal cancer patients is high and sensitive to drug cost. Incremental cost-effectiveness ratios were lower when the analysis was limited to patients with wild-type KRAS tumors.
| CONTEXT AND CAVEATS Prior knowledge The National Cancer Institute of Canada Clinical Trials Group CO.17 study is a randomized study of the epidermal growth factor receptor–targeting antibody cetuximab vs best supportive care among patients with advanced colorectal cancer that showed improved overall survival with cetuximab. The survival advantage was higher for patients whose tumors harbored wild-type KRAS. Study design A cost-effectiveness analysis using prospectively collected resource utilization and health utility data for patients in the CO.17 study who received cetuximab or best supportive care. Mean survival times of the study arms for the entire study population and for patients whose tumors harbored wild-type KRAS were calculated over an 18- to 19-month period. Contribution For all patients in the CO.17 trial, cetuximab showed very high incremental cost-effectiveness ratios (cost per life-year gained and cost per quality-adjusted life-year gained) when compared with best supportive care. The incremental cost-effectiveness ratios were more favorable for patients whose tumors harbored wild-type KRAS but still in excess of $120 000 per life-year gained and $186 000 per quality-adjusted life-year gained. Implications Providing cetuximab only to patients with tumors that express wild-type KRAS has a more favorable cost-effectiveness ratio than treating patients irrespective of tumor KRAS mutation status but still has a high cost-effectiveness ratio. Limitations The results may not be generalizable to all patients under routine care for advanced colorectal cancer. The maximum follow-up in the trial was 1.58 years. The CO.17 trial included patients who had chemorefractory disease, but this is an approved indication for cetuximab. From the Editors
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Manuscript received October 23, 2008; revised June 5, 2009; accepted June 23, 2009.
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