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

Results

Patient Demographics

Five hundred seventy-two patients were accrued to CO.17 (287 to cetuximab). All patients had received prior chemotherapy with a fluoropyrimidine; 98% of patients had received prior treatment with oxaliplatin and 96% had received prior treatment with irinotecan. The KRAS mutation status of the tumor was determined retrospectively for 394 patients (69%; 198 from the cetuximab group and 196 from the best supportive care group); 58% of the tumors had wild-type KRAS (117 from the cetuximab group and 113 from the best supportive care group).[7]

HUI Values

HUI3 values for cetuximab and for best supportive care were recorded over the duration of the trial (Table 1). At each follow-up, mean utility scores for cetuximab were higher than those for best supportive care. For the cetuximab arm, the utility scores remained essentially unchanged at each follow-up. By contrast, utility scores for best supportive care generally declined with time. However, direct interpretation of utility scores is difficult because of survivorship bias as observed by the high utility scores in the last follow-up.

Costs and Economic Analysis for the Entire Study Population

Costs, resources, and cost source information are presented in Table 2. Total costs were higher in the cetuximab arm than in the best supportive care arm, with the incremental cost with cetuximab calculated at $23 969 per patient (Table 3). The mean survival gain with cetuximab was 0.12 years (7.7 months [0.64 years] in the cetuximab arm vs 6.2 months [0.52 years] in the best supportive care arm). The gain in survival for cetuximab compared with best supportive care resulted in a mean incremental cost-effectiveness ratio of $199 742 per life-year gained (95% CI based on the bootstrap analysis = $125 973 to $652 492 per life-year gained) (Figure 1, A, Table 4). Cetuximab resulted in a mean gain of 0.08 QALYs, with a mean incremental cost–utility ratio of $299 613 per QALY gained (95% CI based on the bootstrap analysis = $187 400 to $898 201 per QALY gained) (Figure 1, B, Table 4).

Figure 1.

Economic evaluation of cetuximab therapy in the entire study population. Scatter plot for (A) incremental cost-effectiveness ratios (ICERs) and (B) incremental cost–utility ratios (ICUR) based on bootstrapping. Each point in panels A and B represents one of the 1000 iterations of the bootstrap and represents the mean incremental cost and effectiveness of cetuximab compared with best supportive care. Cost-effectiveness acceptability curves for (C) ICER and (D) ICUR based on the bootstrap plotted in panels A and B. The curves in panels C and D represent the probability cetuximab is cost-effective compared with best supportive care based on a threshold for the incremental cost-effectiveness ratio. QALY = quality-adjusted life-year.

Economic Analysis for the Subset of Patients with Wild-type KRAS Tumors

For the patients whose tumors harbored wild-type KRAS, total costs were higher in the cetuximab arm than in the best supportive care arm, with the incremental cost with cetuximab calculated at $33 617 per patient (Figure 2, A, Table 4). The mean survival gain with cetuximab increased to 0.28 years (9.5 months [0.79 years] in the cetuximab vs 6.1 months [0.51 years] in the best supportive care arm). This gain in survival resulted in a mean incremental cost-effectiveness ratio of $120 061 per life-year gained (95% CI based on the bootstrap analysis = $88 679 to $207 075 per life-year gained) (Figure 2, A, Table 4). The mean number of QALYs gained for cetuximab in this subset analysis was 0.18, with a mean incremental cost–utility ratio of $186 761 per QALY gained (95% CI based on the bootstrap analysis = $130 326 to $334 940 per QALY gained) (Figure 2, B, Table 4).

Figure 2.

Economic evaluation of cetuximab therapy in the subset of patients with wild-type KRAS tumors. Scatter plot for (A) incremental cost-effectiveness ratios (ICERs) and (B) incremental cost–utility ratios (ICURs) based on bootstrapping. Each point in panels A and B represents one of the 1000 iterations of the bootstrap and represents the mean incremental cost and effectiveness of cetuximab compared with best supportive care. Cost-effectiveness acceptability curves for (C) ICER and (D) ICUR based on the bootstrap plotted in panels A and B. The curves in panels C and D represent the probability cetuximab is cost-effective compared with best supportive care based on a threshold for the incremental cost-effectiveness ratio. QALY = quality-adjusted life-year.

Sensitivity Analysis

The incremental cost-effectiveness ratios were most sensitive to changes in the cost of cetuximab and patient survival (Table 5). A sensitivity analysis was performed on every cost, resource, and effectiveness variable. The cost of cetuximab and patient survival were the only variables that were found to influence cost-effectiveness. The remaining variables had minimal impact on the incremental ratios (data not shown). There was no evidence of heterogeneity between countries (data not shown).

For the entire study population, the probability of cetuximab being considered cost-effective was 0% at a threshold value of $50 000 per life-year gained, 0.1% at a threshold value of $100 000 per life-year gained, and 43.4% at a threshold value of $200 000 per life-year gained (Figure 1, C). In the cost-per-QALY case, the probability that cetuximab is cost-effective compared with best supportive care in the entire population is 0 for thresholds of $150 000 per QALY or less (Figure 1, D). At a threshold of $200 000 per QALY, there is only a 3.4% chance that cetuximab is cost-effective compared with best supportive care. For the wild-type KRAS tumor population, the probability of cetuximab being considered cost-effective was 0% at a threshold value of $50 000 per life-year gained, 9.3% at a threshold value of $100 000 per life-year gained, and 96.6% at a threshold value of $200 000 per life-year gained (Figure 2, C). Similarly, at thresholds of $100 000 and $200 000 per QALY, the probabilities of cost-effectiveness for cetuximab compared with best supportive care are 0% and 61%, respectively (Figure 2, D).

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....