Clinical and economic value of screening for Kras mutations as predictors of response to epidermal growth factor receptor inhibitors

Abstract

Purpose: The clinical and economic value of screening for Kras mutations as predictors of response to cetuximab and panitumumab are reviewed.

Summary: Epidermal growth factor receptor (EGFR) inhibitors cetuximab and panitumumab are agents currently used in the treatment of metastatic colorectal cancer. Cetuximab is approved in combination with irinotecan for second-line therapy or as a single agent in the third-line setting, and panitumumab is approved as a single agent for third-line therapy. Historically, response rates to EGFR inhibitors have been low; therefore, predictors of response or lack of response have been highly sought after. Mutations in the Kras oncogene, which encodes for the RAS protein located downstream from EGFR, have been associated with poor response to EGFR inhibitor therapy. Numerous studies have confirmed a Kras mutation frequency in approximately 40% of all metastatic colorectal cancers, as well as an associated lack of response to EGFR inhibitor therapy. Screening for Kras mutations before selecting a therapy may be clinically beneficial by avoiding the cost and toxicity of ineffective therapy. A simple breakeven analysis using a group of 100 hypothetical patients with metastatic colorectal cancer revealed that cost savings will be achieved if screening can be conducted for less than $3460 per patient, regardless of which EGFR inhibitor is used.

Conclusion: Mutations in the Kras oncogene are associated with a poor response to EGFR inhibitor therapy in metastatic colorectal cancer. Implementing routine Kras screening and limiting the use of EGFR inhibitors to patients with wild-type (not mutated) Kras may have the potential for cost savings.