Economic analysis of bevacizumab, cetuximab, and panitumumab with fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC)

Abstract

Objective:

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to human vascular endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild-type patients. Recent evidence has shown clinical benefit from anti-epidermal growth factor treatments cetuximab and panitumumab in these patients. The cost-effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was assessed for first-line treatment of KRAS wild-type mCRC patients.

Methods:

A Markov model was developed and calibrated to progression-free/overall survival, using separately reported trial survival and adverse event results for each comparator. Health-state resource utilization was derived from published data and oncologist input. Utilities and unit prices were obtained from published literature and standard Canadian sources.

Results:

Results per patient are over a lifetime horizon, to a maximum of 10 years, with 5% annual discounting. Comparators are ordered by total cost and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Compared to FBC alone, bevacizumab + FBC has an ICER of $131,600 per QALY gained. Compared to bevacizumab + FBC, panitumumab + FBC is dominated and cetuximab + FBC has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis, bevacizumab + FBC had ∼100%, ∼100%, and 98.9% probabilities of being more cost-effective than both of the other combination treatments at thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively.

Conclusion:

For first-line treatment of KRAS-WT mCRC, bevacizumab + FBC is associated with substantially lower costs as compared to panitumumab + FBC or cetuximab + FBC. Key limitations were that survival curves and adverse event rates were taken from separate clinical trials and that an indirect comparison was not included. Given these findings, bevacizumab is likely to offer the best value for money for this patient population.

Keywords::

• Bevacizumab
• Cost-effectiveness
• Metastatic colorectal cancer
• First-line treatment
• Health economics

Transparency

Declaration of funding

This study was sponsored by Hoffmann-LaRoche Ltd. Hoffmann-LaRoche Ltd reviewed and provided comment on the draft versions of the manuscript and also approved the final version.

Declaration of financial/other relationships

Donna Lawrence, Michael Maschio, Kevin J. Leahy, and Milton C. Weinstein are employees of OptumInsight. OptumInsight was funded by Hoffmann-La Roche to adapt the model and provide editorial support for the manuscript. The authors from OptumInsight did not receive individual payments from Hoffmann-La Roche for their involvement in this study. Simon Yunger is an employee of Hoffmann-La Roche and has stock or other ownership interest in Hoffmann-La Roche. Jacob C. Easaw is an employee of Tom Baker Cancer Center and has received honoraria and research funding from Hoffmann-La Roche. JME Peer Reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Dr Natalie Aucoin (NA) and Dr Kelvin Chan (KC) for their input in Canadian resource utilization and recommendations for treatment of adverse events.