Cost-effectiveness of screening for KRAS and BRAF mutations in metastatic colorectal cancer
Screening cost effective; anti-EGFR treatment costly
- Date : 07 Feb 2013
- Topic : Gastrointestinal cancers
Advances in treatments and molecular testing have improved the outcomes of patients with metastatic colorectal cancer (mCRC). Since 2009, it has been recommended that patients with mCRC, who are candidates for anti-epidermal growth factor receptor (EGFR) therapy have their tumours tested for KRAS mutations because tumours with such mutations do not respond to anti-EGFR therapy. Thus, limiting anti-EGFR therapy to those without KRAS mutations would reserve treatment for those likely to benefit, and avoid unnecessary exposure to harmful and costly treatment in those who would not. Similarly, tumours with BRAF genetic mutations may not respond to anti-EGFR therapy, although this is less clear.
Ajay Behl, PhD of the HealthPartners Research Foundation in Bloomington, USA and colleagues decided to evaluate the comparative effectiveness of screening for KRAS and BRAF mutations in patients with mCRC. Previous economic analyses of mutation testing have not fully explored the roles of alternative therapies, resection of metastases, and survival for the different types of metastases.
The research by Behl and his colleagues was based on a decision analytic framework that forms the basis of a cost-effectiveness analysis of screening for KRAS and BRAF mutations in mCRC in the context of treatment with cetuximab. It included parameters based on the available evidence from clinical trials and other literature. A cohort of 50,000 patients with mCRC was simulated 10,000 times, with attributes randomly assigned on the basis of distributions from randomised controlled trials.
This comprehensive research programme had two main components: first, secondary data collection through evidence synthesis and cost-effectiveness analysis, and second, primary data collection through a proof-of-principle study to examine questions about personalised medicine for CRC.
The results show that the screening for both KRAS and BRAF mutations compared with the base strategy (of no anti-EGFR therapy) increases expected overall survival by 0,034 years at a cost of 22,033 USD, yielding an incremental cost-effectiveness ratio of approximately 650,000 USD per additional year of life. Compared with anti-EGFR therapy without screening, adding KRAS testing saves approximately 7,500 USD per patient; adding BRAF testing saves another 1,023 USD, with little reduction in expected survival.
The results of this study revealed that anti-EGFR treatment is costly. Screening for KRAS and BRAF mutations can substantially reduce the cost of providing anti-EGFR treatment with a very small reduction in overall survival. According to the authors, “crucially, the results are less supportive of the use of anti-EGFR treatment than earlier research has shown. We cannot confirm that anti-EGFR treatment is a cost-effective use of health-care resources. However, KRAS testing is cost saving, with BRAF testing likely to offer additional savings.” In the future, Behl's team plans “to use these data to analyse differences in the treatment of mCRC in rural and urban health-care settings.”
In conclusion, screening for KRAS and BFAF mutation improves the cost-effectiveness of anti-EGFR therapy, but the incremental cost effectiveness ratio remains above the generally accepted threshold for acceptable cost effectiveness ratio of 100,000/quality adjusted life year.
The authors published their findings in the Journal of National Cancer Institute.
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