Epidermal Growth Factor Receptor (EGFR) Mutation Analysis for Individuals with Non-Small Cell Lung Cancer (NSCLC)
DESCRIPTION
Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (TK), is frequently overexpressed and activated in non-small cell lung cancer (NSCLC). The EGFR gene, Mutations in two regions of the EGFR gene (which includes exons 18-24) appear to predict tumor response to tyrosine kinase inhibitors (TKIs), such as erlotinib or gefitinib. These are small deletions in exon 19 and a point mutation in exon 21 (L858R).
POLICY
Analysis of somatic mutations of the epidermal growth factor receptor gene is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Analysis of somatic mutations of the epidermal growth factor receptor gene, including but not limited to the following, is considered investigational:
Other mutations within exons 18-24
Other applications related to NSCLC
MEDICAL APPROPRIATENESS
Analysis of somatic mutations of the epidermal growth factor receptor is considered medically appropriate with ALL of the following criteria:
Individual with advanced non-small cell lung cancer
Cancer is not associated with squamous cell type
Used to predict treatment response to TKIs (e.g., erlotinib or gefitinib)
Analysis of ANY ONE of the following:
Small deletions in exon 19
Point mutation in exon 21 (L858R)
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
There is a lack of evidence to support the analysis of somatic mutations of the epidermal growth factor receptor gene, in exons other than exon 19 and exon 21, to determine treatment response.
Two EGFR tyrosine kinase inhibitor (TKI) drugs, erlotinib and gefitinib, have been approved by the U.S. Food and Drug Administration (FDA). Erlotinib (Tarceva®) received approval from the U.S. Food and Drug Administration (FDA) in November 2004 as salvage therapy for advanced NSCLC, based on results of a phase III clinical trial. Gefitinib (Iressa®) was approved by the FDA in 2003 through the agency’s accelerated approval process, based on the initially promising results of phase II trials. The labeled indication was limited to patients with NSCLC who had failed 2 or more prior chemotherapy regimens. However, in December 2004, results of phase III trials became available, suggesting that gefitinib was not associated with a survival benefit. In the press release, the FDA noted that in phase III trials patients treated with erlotinib did have a very modest, but statistically significant improvement in survival, implying that this was the preferred agent. In May 2005, the FDA revised the labeling of gefitinib to further limit its use to patients who were currently benefiting from the drug, or who had benefited in the past.
Subgroup analyses of clinical trials of both of these drugs suggested that factors predicting response were female sex, never having smoked, Asian descent, or bronchioalveolar cancer (as opposed to other NSCLC histologies). Several studies subsequently reported that these characteristics are associated with somatic mutations in the EGFR gene TK ATP-binding domain, suggesting that mutational analysis potentially could be used to predict sensitivity to these targeted therapies.
EGFR gene mutation analysis is now commercially available through Genzyme Genetics. Somatic or EGFR mutation analysis is offered as a laboratory-developed test. The FDA does not regulate these. Laboratories performing these tests must meet quality standards as prescribed under the Clinical Laboratory Improvement Amendments (CLIA).
SOURCES
Azzoli, C. G., Baker, S. Jr., Temin, S., Pao, W., Aliff, T., Brahmer, J., et al. (2009). American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. Retrieved June 30, 2011 from http://jco.ascopubs.org/content/27/36/6251.full.
BlueCross BlueShield Association. Medical Policy Reference Manual. (1:2011). Epidermal growth factor receptor (EGFR) mutation analysis for patients with non-small cell lung cancer (NSCLC) (2.04.45).Retrieved May 11, 2011 from BlueWeb. (30 articles and/or guidelines reviewed)
Hirsch, F.R., Varella-Garcia, M., Bunn, P.A. Jr., Franklin, W.A., Dziadziuszko, R., Thatcher, N., et al. (2007). Molecular predictors of outcome with gefitinib in phase III placebo controlled study in advanced non-small-cell lung cancer. Journal of Clinical Oncology, 24 (31), 5034-5042. (Level 1 Evidence - Industry sponsored)
National Comprehensive Cancer Network. (2011, March). NCCN clinical practice guidelines in oncology. Non-small cell lung cancer (V.3.2011). Retrieved March 4, 2011 from http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
National Institute for Health and Clnical Excellence (NICE). (2010, July). Gefitinib for the first-line treatment of locally advanced or metastatic non-small-cell lung cancer. Retrieved June 29, 2011 from www.nice.org.uk/guidance/TA192.
Technology Evaluation Center. (2011, March). Epidermal growth factor receptor mutations and tyrosine kinase inhibitor therapy in advanced non-small-cell-lung cancer. (Vol. 25, No. 6). Chicago: BlueCross BlueShield Association. (78 articles and/or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 2/10/2008
MOST RECENT REVIEW DATE: 11/12/2011
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