Epidermal Growth Factor Receptor (EGFR) Mutation Analysis for Individuals with Non-Small Cell Lung Cancer (NSCLC)
Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is frequently overexpressed and activated in non-small cell lung cancer (NSCLC). Mutations in two regions of the EGFR gene, which includes exons 18-24, appear to predict tumor response to tyrosine kinase inhibitors (TKIs). These are small deletions in exon 19 and a point mutation in exon 21 (L858R). Tumors with an acquired exon 20 (T790M) substitution mutation appear to respond to osimertinib following failure of TKI therapy.
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 for other applications related to non-small cell lung cancer is considered investigational.
Analysis of somatic mutations of the epidermal growth factor receptor gene is considered medically appropriate for ANY ONE of the following:
To predict treatment response to TKIs (e.g., erlotinib, gefitinib, afatinib) if ALL the following are met:
Individual with advanced non-small cell lung cancer
Cancer is not associated with squamous cell type
Analysis of ANY ONE of the following:
Small deletions in exon 19
Point mutation in exon 21 (L858R)
To predict treatment response to second line medication [i.e., osimertinib (Tagrisso)] if ALL the following are met:
Analysis of exon 20 for T790M mutation
Disease has progressed during or after TKI therapy
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
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.
Three orally administered EGFR-selective, small-molecule TKIs have been identified for treating NSCLC: gefitinib (Iressa®; AstraZeneca), erlotinib (Tarceva®; OSI Pharmaceuticals),5 and afatinib (Gilotrif™; Boehringer Ingelheim).6 Gefitinib, erlotinib, and afatinib currently are approved by the U.S. Food and Drug Administration (FDA) for NSCLC. Although gefitinib was originally approved by FDA, a 2004 phase 3 trial suggested that the drug was not associated with a survival benefit. In May 2005, FDA revised gefitinib labeling further limiting its use to patients who had previously benefitted or were currently benefiting from the drug; no new patients were to be given gefitinib. However, in July 2015, FDA approved gefitinib as first-line treatment for metastatic NSCLC in patients whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.
BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2017). Molecular Analysis for Targeted Therapy of Non-Small-Cell Lung Cancer (2.04.45). Retrieved December 8, 2017 from BlueWeb. (115 articles and/or guidelines reviewed)
Chang, G., Tseng, C., Hsu, K., Yu, C., Yang, C., Chen, K, et al. (2017, February) Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer - a multicenter retrospective SEQUENCE study. Lung Cancer, 104, 58-64. Abstract retrieved December 8, 2017 from PubMed database.
College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. (June, 2013). Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors. Retrieved December 8, 2017 from the National Guideline Clearinghouse (NGC: 9787).
Institute for Clinical and Economic Review. (2016). Treatment options for advanced non-small cell lung cancer: effectiveness, value and value-based price benchmarks. Retrieved November 2, 2016 from https://icer-review.org/material/nsclc-final-report/.
National Comprehensive Cancer Network. (2017, November). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Non-Small Cell Lung Cancer. Version 1.2018. Retrieved December 8, 2017 from www.nccn.org.
National Institute for Health and Care Excellence. NICE Diagnostics Guidance 9. (2013, August). EGFR-TK Mutation Testing in Adults with Locally Advanced or Metastatic Non-Small-Cell Lung Cancer. Retrieved August 18, 2014 from https://www.nice.org.uk/guidance.
Sullivan, I. and Planchard, D. (2016, October) Osimertinib in the treatment of patients with epidermal growth factor receptor T790M mutation-positive metastatic non-small cell lung cancer: clinical trial evidence and experience. Therapeutic Advances in Respiratory Diseases, pii 1753465816670498. [Epub ahead of print]. Abstract retrieved December 8, 2017 from PubMed database.
U.S. Food and Drug Administration. (2016, June). Center for Devices and Radiological Health. Premarket approval decisions for June 2016. Retrieved November 2, 2016 from http://www.accessdata.fda.gov.
Winifred S. Hayes, Inc. Genetic Test Evaluation (GTE) Report. (2012, February; last update search February 2014). Epidermal growth factor receptor (EGFR) sequence variant analysis for predicting response to non-small cell lung cancer (NSCLC) drug therapy. Retrieved November 2, 2016 from www.Hayesinc.com/subscribers. (203 articles and/or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 2/10/2008
MOST RECENT REVIEW DATE: 1/25//2018
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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