A cost-effectiveness analysis of two anti-EGFR monoclonal antibodies (cetuximab and panitumumab) plus best supportive care versus best supportive care alone as third-line treatment of advanced chemorefractory metastatic colorectal cancer

ABSTRACT Introduction The National Cancer Institute of Canada Clinical Trials Group CO. 17 trial and the Open-Label Phase III trial showed that the addition of new anti-EGFR monoclonal antibodies (cetuximab andpanitumumab) to best supportive care as third-line treatments prolong the life of patients with advanced metastatic colorectal cancer, but have also introduced a unique set of toxicities and increased costs. In a resource constrained environment this prompts the need for tools to identify the patients who are likely to benefit from these therapies in a more efficient and cost-effective way. We developed an economic model using analytic decision modeling to assess the cost-effectiveness of two anti-EGFR monoclonal antibodies (cetuximab and panitumumab) plus best supportive care versus best supportive care alone as third-line treatment in advanced chemorefractory metastatic colorectal cancer. Methods We constructed a Markov model based on the efficacy data obtained from the National Cancer Institute of Canada Clinical Trials Group CO. 17 trial and the Open-Label Phase III trial studies. Costs for physician visits, blood products, emergency department visits, hospitalizations and toxicity management were obtained published literature and expert opinion. Drug costs were obtained from London Health Sciences Center (LHSC) drug formulary intranet. The primary outcome of the model is the incremental cost-utility ratio of adding anti-EGFR monoclonal antibodies (panitumumab and cetuximab) to best supportive care as third-line therapies in treatment of advanced metastatic chemo-refractory colorectal cancer, expressed as cost per quality-adjusted life year (QALY) gained. A series of deterministic and probabilistic sensitivity analyses were also performed to account for uncertainty in the model parameters. Results Adding panitumumab to best supportive care (with KRAS test) resulted in a mean gain of 0.087 QALYs with a mean incremental cost utility ratio of $269,703 per QALY gained (95% Cl = $135,432 to $766,072 per QALY gained). The addition of cetuximab to best supportive care (with KRAS test) resulted in a mean gain of 0.068 QALYs with a mean incremental cost-utility ratio of $352,046 per QALY gained (95% Cl = $151,916 to $949,342 per QALY gained). In subset of patients with wild-type KRAS, the addition of panitumumab to best supportive care resulted in a mean gain of 0.16 QALYs with a mean incremental cost-utility ratio of $236,469 per QALY gained (95% Cl = $125,259 to $557,750 per QALY gained). Conclusions From a health economic perspective, both anti-EFGR therapies (panitumumab and cetuximab) showed very high Incremental cost-utility ratios and were not cost-effective at a willingness-to-pay threshold of $100,000 per QALY. The cost-utility ratios were much more favorable in subset of patients with wild-type KRAS. This suggests that personalizing advanced metastatic colorectal cancer treatment based on KRAS mutation status could not only save health care system substantial sums but also spare thousands of patients with metastatic colorectal cancer from side effects of the anti-EGFR therapies that are unlikely to benefit from the treatment