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. ()
(No Recommendation)
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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. ()
(No Recommendation)
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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. ()
(No Recommendation)
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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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Recommendation Grading

Overview

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

Supplemental Implementation Tools

Document Type

Guideline

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