Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

TLDR

In 2013, a guideline by CAP, IASLC, and AMP established standards for molecular analysis of lung cancers to guide targeted therapy, and recent evidence now prompts evaluation of new technologies, genes, patient groups, and tumor types. The objective was to systematically review and update the 2013 guideline, assessing new genetic discoveries, technologies, and therapies to issue an evidence‑based update. An expert panel from CAP, IASLC, and AMP convened to develop the guideline, defining key questions, conducting literature searches, reviewing studies, and drafting recommendations. The panel drafted 18 new recommendations and updated 3 from 2013, reaffirming the guideline while adding cytology testing, higher assay sensitivity, and discouraging IHC for EGFR, and introducing ROS1 testing for all adenocarcinomas, expanded NGS gene panels (ERBB2, MET, BRAF, KRAS, RET), IHC as an alternative to FISH for ALK/ROS1, 5% sensitivity assays for EGFR T790M, and cfDNA testing when tissue is limited.

Abstract

Context.— In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. Objective.— To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. Design.— The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. Results.— Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. Conclusions.— The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to “rule in” targetable mutations when tissue is limited or hard to obtain.