Coverage Policy Manual
Policy #: 2013007
Category: Laboratory
Initiated: January 2013
Last Review: February 2019
  Genetic Test: Head and Neck Cancer, EGFR Mutation Analysis to Predict Sensitivity to Chemotherapy

Description:
Description
Epidermal growth factor receptor is commonly overexpressed in cancers of the head and neck. Cetuximab is a monoclonal antibody that works by blocking the EGFR receptor. In March 2006, cetuximab was approved by the U.S. Food and Drug Administration for unresectable squamous cell head and neck cancer with radiation therapy and as a single agent for metastatic head and neck cancer. In November 2011, cetuximab was approved for use with other drugs for head and neck cancer. Although, EGFR mutation analysis has been studied as a screening test to predict response to anti-EGFR agents in patients with head and neck cancer (Murray, 2010), the FDA approval does not require assessment of EGFR expression prior to treatment with cetuximab in patients with head and neck cancer.
 
EGFR mutational analysis is commercially available at several commercial reference laboratories.
  
Coding
Effective in 2013, there is a specific CPT code for testing for common variants of EGFR:
 
81235: EGFR (epidermal growth factor receptor) (e.g., non-small cell lung cancer) gene analysis, common variants (e.g., exon 19 LREA deletion L858R, T790M, G719A, G719S, L861Q)
 
 

Policy/
Coverage:
Epidermal Growth Factor Receptor (EGFR) mutation analysis to predict sensitivity to chemotherapy for the treatment of head and neck cancer does not meet member benefit certificate primary coverage criteria because there is a lack of scientific evidence that this testing improves health outcomes.
 

Rationale:
EGFR mutation analysis has been studied as a screening test to predict response to anti-EGFR agents in patients with head and neck cancer. In 2010, Murray and colleagues reported results of a prospective compassionate-use study evaluating the correlation between EGFR mutation status with response to treatment with gefitinib in patients with head and neck cancer.(Murray, 2010). EGFR mutations were detected in six out of nineteen patients treated with gefitinib. No significant differences were reported in time to disease progression or overall survival for patients with somatic EFGR mutations.
 
The EXTREME Trial (Vermorken, 2008) which evaluated the benefit of adding cetuximab to standard platinum based therapy for the treatment of head and neck cancer included a subgroup analysis of the benefit of EGFR testing. Although the addition of cetuximab improved overall survival significantly, the subgroup analysis found that there was similar improved survival benefit in the cetuximab group for those who were EGFR negative versus those who were EGFR positive.
 
At present, cetuximab is the only anti-EGFR agent approved for the treatment of head and neck cancer. In a review article (Egloff, 2009) discussing the response rates to EGFR-targeted therapies for squamous cell carcinoma of the head and neck, the author states, “”expression levels of EGFR in the tumor have not correlated with response to cetuximab and no single biomarker to date in baseline tissue has been proven to predict response to EGFR targeting agents.” No randomized controlled trials assessing the correlation between EGFR expression and response to cetuximab published after this review have been identified.
 
The NCCN guideline for the treatment of Head and Neck Cancer (V.1.2012) does not mention testing for EGFR mutation status prior to treatment with anti-EGFR agents.
 
2014 Update
A literature search was conducted using the MEDLINE database through January 2014. There was no new literature that would prompt a change in the coverage statement.
 
2015 Update
A literature search conducted through January 2015 did not reveal any new information that would prompt a change in the coverage statement.
 
2016 Update
A literature search was conducted through December 2015 using the MEDLINE database. There was no new randomized controlled trials or other new information identified that would prompt a change in the coverage statement.  
 
2017 Update
There were no randomized controlled trials identified that would prompt a change in the coverage statement. One trial to assess the use of erlotinib in the prevention of oral cancer was identified (William, 2016). This trial used level of heterozygosity (LOH) profiles as a measure of risk stratification. Increased EGFR gene copy number correlated with LOH-positive status (P < .001) and lower CFS (P = .01). In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in clinical practice but do not support erlotinib use in this setting. The results of this study do not prompt a change in the coverage statement.
 
2018 Update
A literature search conducted through January 2018 revealed no new information that would prompt a change in the coverage statement.
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2019. No new literature was identified that would prompt a change in the coverage statement.  

CPT/HCPCS:
81235EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q)
81479Unlisted molecular pathology procedure

References: Egloff AM and Grandis JR.(2009) Improving response rates to EGFR-targeted therapies for head and neck squamous cell carcinoma: candidate predictive biomarkers and combination treatment with Src inhibitors. J Oncol. Volume 2009.

Egloff AM and Grandis JR.(2009) Improving rsponse rates to EGFR-targeted therapies for head and neck squamous cell carcinoma: candidate predictive biomarkers and combination treatment with Src inhibitors. J Oncol. Volume 2009. Epub 2009 Jul 14.

Murray S., Bobos M., Angouridakis N. et al.(2011) Screening for EGFR mutations in patients with head and neck cancer treated with gefitinib on a compassionate-use program: a hellenic cooperative oncology group study. J Oncol. Volume 2010. Epub 2011 Jan. 3.

NCCN Clinical Practice Guidelines in Oncology. Head and Neck Cancer. Version 1.2012. Available at NCCN.org. Last accessed February 12, 2013.

Vermorken JJB, Mesia R., Rivera F. et al.(2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27.

William WN. Jr, Papadimitrakopoulou V, MD, Lee JJ., et al.(2016) Erlotinib and the Risk of Oral Cancer: The Erlotinib Prevention of Oral Cancer (EPOC) Randomized Clinical Trial. JAMA Oncol. 2016 Feb;2(2):209-16.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.