Prospective Cost-effectiveness Analysis of Cetuximab in Metastatic Colorectal Cancer: Evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 Trial

Evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 Trial

Nicole Mittmann; Heather-Jane Au; Dongsheng Tu; Christopher J. O'Callaghan; Pierre K. Isogai; Christos S. Karapetis; John R. Zalcberg; William K. Evans; Malcolm J. Moore; Jehan Siddiqui; Brian Findlay; Bruce Colwell; John Simes; Peter Gibbs; Matthew Links; Niall C. Tebbutt; Derek J. Jonker

Disclosures

J Natl Cancer Inst. 2009;101(17):1182-1192. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

Colorectal cancer is the second leading cause of cancer death in Canada,[1] affecting men and women in equal numbers. In Canada, it has been estimated that 21 500 new cases of colorectal cancer would be diagnosed in 2008, and 8900 deaths from this disease would occur.[1] Although substantial advances have been made in the management of colorectal cancer, the prognosis remains poor for patients with advanced disease and treatment for these patients is limited to supportive care options.

Several randomized trials have demonstrated that therapy with cetuximab, a monoclonal antibody inhibitor of the epidermal growth factor receptor (EGFR),[2] improves a variety of clinically important outcomes in patients with advanced colorectal cancer.[3–5] Post hoc exploratory analyses of these studies have suggested that the benefits of cetuximab are limited to patients whose tumors harbor a wild-type KRAS gene.[6–8] The presence of activating mutations in KRAS, which encodes a G protein essential in downstream signaling of the EGFR pathway, appears to allow tumor cells to proliferate in the presence of cetuximab inhibition of EGFR.[8–17]

National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) CO.17 (hereafter called CO.17; ClinicalTrials.gov identifier: NCT00079066) was a multicenter (Canada and Australia), open-label, randomized phase III trial of cetuximab plus best supportive care vs best supportive care alone in patients with chemotherapy-refractory metastatic EGFR-positive colorectal cancer. CO.17 demonstrated a clinically and statistically significant overall survival advantage for cetuximab in this population of patients with metastatic disease (median survival for cetuximab vs best supportive care: 6.1 months [0.51 years] vs 4.6 months [0.38 years], hazard ratio [HR] for death = 0.77, P = .005).[4] The survival advantage was even greater in the subset of patients with wild-type KRAS tumors (median overall survival for cetuximab vs best supportive care: 9.5 months [0.79 years] vs 4.8 months [0.4 years], HR for death = 0.55, P < .001).[7]

Despite these benefits, targeted therapies such as cetuximab are likely to increase the already substantial economic burden associated with the management of colorectal cancer. The evaluation of the cost-effectiveness and cost utility of target therapies is of substantial interest to health-care providers, policy makers, and funders. Here, we report the incremental cost-effectiveness (cost per life-year gained and cost per quality-adjusted life-year [QALY] gained) of cetuximab plus best supportive care vs best supportive care alone, from the perspective of the Canadian health-care system, for the entire CO.17 study population and for the study participants whose tumors harbored wild-type KRAS.

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