EGFR Testing
Analysis of tumor tissue for somatic variants in exons 18 through 21 (eg, G719X, L858R, T790M, S6781, L861Q) within the epidermal growth factor receptor (EGFR) gene, may be considered medically necessary to predict treatment response to a U.S. Food and Drug Administration (FDA) -approved therapy (eg, erlotinib [Tarceva] alone or in combination with ramucirumab [Cyramza], gefitinib [Iressa], afatinib [Gilotrif], dacomitinib [Vizimpro], or osimertinib [Tagrisso]) in individuals with advanced lung adenocarcinoma, large cell carcinoma, advanced squamous-cell non-small-cell lung cancer (NSCLC), and NSCLC not otherwise specified, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines).
Analysis of tumor tissue for somatic variants in exon 20 (eg, insertion mutations) within the EGFR gene, may be considered medically necessary to predict treatment response to an FDA-approved therapy (eg, mobocertinib [Exkivity]) in individuals with NSCLC, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines).
At diagnosis, analysis of plasma for somatic variants in exons 19 through 21 (eg, exon 19 deletions, L858R, T790M) within the EGFR gene, using an FDA-approved companion diagnostic plasma test to detect circulating tumor DNA (ctDNA) may be considered medically necessary as an alternative to tissue biopsy (see Policy Guidelines) to predict treatment response to an FDA-approved therapy in individuals with advanced lung adenocarcinoma, large cell carcinoma, advanced squamous cell NSCLC, and NSCLC not otherwise specified, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines).
At progression, analysis of plasma for the EGFR T790M resistance variant for targeted therapy with osimertinib using an FDA-approved companion diagnostic plasma test to detect ctDNA may be considered medically necessary in individuals with advanced lung adenocarcinoma, large cell carcinoma, advanced squamous cell NSCLC, and NSCLC not otherwise specified, when tissue biopsy to obtain new tissue is not feasible (eg, in those who do not have enough tissue for standard molecular testing using formalin-fixed paraffin-embedded tissue, do not have a biopsy-amenable lesion, or cannot undergo biopsy), and when the individual does not have any FDA-labeled contraindications to osimertinib and it is intended to be used consistently with the FDA-approved label (see Policy Guidelines).
Analysis of somatic variants in the EGFR gene in tissue or plasma, including variants within exons 22 to 24, is considered investigational in all other situations.
ALK Testing
Analysis of tumor tissue for somatic rearrangement variants of the anaplastic lymphoma kinase (ALK) gene in tissue may be considered medically necessary to predict treatment response to an FDA-approved ALK inhibitor therapy (eg, crizotinib [Xalkori], ceritinib [Zykadia], alectinib [Alecensa], brigatinib [Alunbrig], or lorlatinib [Lorbrena]) in individuals with advanced lung adenocarcinoma or in whom an adenocarcinoma component cannot be excluded, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines ).
Analysis of plasma for somatic rearrangement variants of the ALK gene using an FDA-approved companion diagnostic plasma test to detect ctDNA may be considered medically necessary as an alternative to tissue biopsy (see Policy Guidelines) to predict treatment response to an FDA-approved ALK inhibitor therapy in individuals with NSCLC (eg, alectinib [Alcensa]), if the individual does not have any FDA-labeled contraindications to the requested agent and both the agent and ctDNA test are intended to be used consistently with their FDA-approved labels (see Policy Guidelines).
Analysis of somatic rearrangement variants of the ALK gene in tissue or plasma is considered investigational in all other situations.
BRAF V600E Testing
Analysis of tumor tissue for the somatic BRAF V600E variant may be considered medically necessary to predict treatment response to an FDA-approved BRAF and/or MEK inhibitor therapy (eg, dabrafenib [Tafinlar] and trametinib [Mekinist]), in individuals with advanced lung adenocarcinoma or in whom an adenocarcinoma component cannot be excluded, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines ).
Analysis of tumor tissue for the somatic BRAF V600E variant is considered investigational in all other situations.
Analysis of plasma for the somatic BRAF V600E variant to detect ctDNA is considered investigational as an alternative to tissue biopsy (see Policy Guidelines) to predict treatment response to BRAF and/or MEK inhibitor therapy (eg, dabrafenib [Tafinlar], trametinib [Mekinist]) in individuals with NSCLC.
ROS1 Testing
Analysis of tumor tissue for somatic rearrangement variants of the ROS1 gene may be considered medically necessary to predict treatment response to an FDA-approved ROS1 inhibitor therapy (eg, crizotinib [Xalkori] ) in individuals with advanced lung adenocarcinoma or in whom an adenocarcinoma component cannot be excluded, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines).
Analysis of tumor tissue for somatic rearrangement variants of the ROS1 gene is considered investigational in all other situations.
Analysis of plasma for somatic rearrangement variants of the ROS1 gene to detect ctDNA is considered investigational as an alternative to tissue biopsy (see Policy Guidelines) to predict treatment response to ROS1 inhibitor therapy (eg, crizotinib [Xalkori] or entrectinib ) in individuals with NSCLC.
KRAS Testing
Analysis of tumor tissue for somatic variants of the KRAS gene (eg, G12C) may be considered medically necessary to predict treatment response to sotorasib (Lumakras) in individuals with advanced lung adenocarcinoma or in whom an adenocarcinoma component cannot be excluded, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines ).
Analysis of plasma for somatic variants of the KRAS gene (eg, G12C) using an FDA-approved companion diagnostic plasma test to detect ctDNA may be considered medically necessary as an alternative to tissue biopsy (see Policy Guidelines) to predict treatment response to sotorasib (Lumakras) in individuals with advanced lung adenocarcinoma or in whom an adenocarcinoma component cannot be excluded, if the individual does not have any FDA-labeled contraindications to the requested agent and both the agent and ctDNA test are intended to be used consistently with their FDA-approved labels (see Policy Guidelines).
All other uses of analysis of somatic variants of the KRAS gene in tissue or plasma are considered investigational.
RET Rearrangement Testing
Analysis of tumor tissue for somatic alterations in the RET gene may be considered medically necessary to predict treatment response to RET inhibitor therapy (e.g., pralsetinib (Gavreto) or selpercatinib (Retevmo) in individuals with metastatic NSCLC, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines).
Analysis of tumor tissue for somatic alterations in the RET gene is considered investigational in all other situations.
Analysis of plasma for somatic alterations of the RET gene using plasma specimens to detect ctDNA is considered investigational as an alternative to tissue biopsy (see Policy Guidelines) to predict treatment response to RET inhibitor therapy (eg, selpercatinib [Retevmo], pralsetinib [Gavreto]) in individuals with NSCLC.
MET Exon 14 Skipping Alteration
Analysis of tumor tissue for somatic alterations in tissue that leads to MET exon 14 skipping may be considered medically necessary to predict treatment response to capmatinib (Tabrecta) in individuals with metastatic NSCLC, if the individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label (see Policy Guidelines).
Analysis of plasma for somatic alteration that leads to MET exon 14 skipping using an FDA-approved companion diagnostic plasma test to detect ctDNA may be considered medically necessary as an alternative to tissue biopsy (see Policy Guidelines) to predict treatment response to MET inhibitor therapy (eg, capmatinib [Tabrecta]) in individuals with NSCLC, if the individual does not have any FDA-labeled contraindications to the requested agent and both the agent and ctDNA test are intended to be used consistently with their FDA-approved labels (see Policy Guidelines).
All other uses of analysis of somatic variants of the MET gene in tissue or plasma are considered investigational.
Plasma Testing When Tissue is Insufficient
Plasma tests for oncogenic driver variants deemed medically necessary on tissue biopsy may be considered medically necessary to predict treatment response to targeted therapy for individuals meeting the following criteria:
Individual does not have sufficient tissue for standard molecular testing using formalin-fixed paraffin-embedded tissue; AND
Follow-up tissue-based analysis is planned should no driver variant be identified via plasma testing.
Testing for other variants may become available between policy updates.
