Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment with Targeted Tyrosine Kinase Inhibitors
Publication Date: March 28, 2018
Last Updated: March 14, 2022
Recommendations
Which new genes should be tested for lung cancer patients?
ROS1 testing must be performed on all lung adenocarcinoma patients, irrespective of clinical characteristics. (S)
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ROS1 IHC may be used as a screening test in lung adenocarcinoma patients; however, positive ROS1 IHC results should be confirmed by a molecular or cytogenetic method. (EC)
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BRAF molecular testing is currently not indicated as a routine stand-alone assay outside the context of a clinical trial. It is appropriate to include BRAF as part of larger testing panels performed either initially or when routine EGFR, ALK, and ROS1 testing are negative. (EC)
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RET molecular testing is not recommended as a routine stand-alone assay outside the context of a clinical trial. It is appropriate to include RET as part of larger testing panels performed either initially or when routine EGFR, ALK, and ROS1 testing are negative. (EC)
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ERBB2 (HER2) molecular testing is not indicated as a routine stand-alone assay outside the context of a clinical trial. It is appropriate to include ERBB2 (HER2) mutation analysis as part of a larger testing panel performed either initially or when routine EGFR, ALK, and ROS1 testing are negative. (EC)
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KRAS molecular testing is not indicated as a routine stand-alone assay as a sole determinant of targeted therapy. It is appropriate to include KRAS as part of larger testing panels performed either initially or when routine EGFR, ALK, and ROS1 testing are negative. (EC)
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MET molecular testing is not indicated as a routine stand-alone assay outside the context of a clinical trial. It is appropriate to include MET as part of larger testing panels performed either initially or when routine EGFR, ALK, and ROS1 testing are negative. (EC)
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What methods should be used to perform molecular testing?
IHC is an equivalent alternative to FISH for ALK testing. (R)
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Multiplexed genetic sequencing panels are preferred over multiple single-gene tests to identify other treatment options beyond EGFR, ALK, and ROS1. (EC)
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Laboratories should ensure test results that are unexpected, discordant, equivocal, or otherwise of low confidence are confirmed or resolved using an alternative method or sample. (EC)
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Is molecular testing appropriate for lung cancers that do not have an adenocarcinoma component?
Physicians may use molecular biomarker testing in tumors with histologies other than adenocarcinoma when clinical features indicate a higher probability of an oncogenic driver. (EC)
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What testing is indicated for patients with targetable mutations who have relapsed on targeted therapy?
In lung adenocarcinoma patients who harbor sensitizing EGFR mutations and have progressed after treatment with an EGFR-targeted TKI, physicians must use EGFR T790M mutational testing when selecting patients for third-generation EGFR-targeted therapy. (S)
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Laboratories testing for EGFR T790M mutation in patients with secondary clinical resistance to EGFR-targeted kinase inhibitors should deploy assays capable of detecting EGFR T790M mutations in as little as 5% of viable cells. (R)
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There is currently insufficient evidence to support a recommendation for or against routine testing for ALK mutational status for lung adenocarcinoma patients with sensitizing ALK mutations who have progressed after treatment with an ALK-targeted TKI. ()
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What is the role of testing for circulating cell-free DNA for lung cancer patients?
There is currently insufficient evidence to support the use of circulating cfDNA molecular methods for the diagnosis of primary lung adenocarcinoma. ()
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In some clinical settings in which tissue is limited and/or insufficient for molecular testing, physicians may use a cfDNA assay to identify EGFR mutations. (R)
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Physicians may use cfDNA methods to identify EGFR T790M mutations in lung adenocarcinoma patients with progression or secondary clinical resistance to EGFR-targeted TKI; testing of the tumor sample is recommended if the plasma result is negative. (EC)
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There is currently insufficient evidence to support the use of circulating tumor cell molecular analysis for the diagnosis of primary lung adenocarcinoma, the identification of EGFR or other mutations, or the identification of EGFR T790M mutations at the time of EGFR TKI resistance. ()
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Updated Statements
Pathologists may use either cell blocks or other cytologic preparations as suitable specimens for lung cancer biomarker molecular testing. (R)
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Laboratories should use, or have available at an external reference laboratory, clinical lung cancer biomarker molecular testing assays that are able to detect molecular alterations in specimens with as little as 20% cancer cells. (EC)
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Laboratories should not use total EGFR expression by IHC testing to select patients for EGFR-targeted TKI therapy. (S)
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Title
Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment with Targeted Tyrosine Kinase Inhibitors
Authoring Organizations
College of American Pathologists
International Association for the Study of Lung Cancer
Endorsing Organization
American Society of Clinical Oncology
Publication Month/Year
March 28, 2018
Last Updated Month/Year
June 7, 2023
External Publication Status
Published
Country of Publication
US
Document Objectives
Critically appraise and endorse the updated CAP/IASLC/AMP guideline on molecular testing for selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors.
Target Patient Population
Patients with advanced lung cancer
Inclusion Criteria
Female, Male, Adult, Older adult
Health Care Settings
Hospital, Laboratory services, Long term care, Operating and recovery room, Outpatient
Intended Users
Radiology technologist, laboratory technician, nurse, nurse practitioner, physician, physician assistant
Scope
Assessment and screening, Management, Treatment
Diseases/Conditions (MeSH)
D008175 - Lung Neoplasms
Keywords
lung cancer, targeted tyrosine kinase inhibitor therapy
Methodology
Number of Source Documents
263
Literature Search Start Date
May 17, 2015
Literature Search End Date
June 27, 2016