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IASLC ATLAS OF ALK TESTING IN LUNG CANCER
Appendix 2
CAP/IASLC/AMP Molecular Testing Guideline for Selection of Patients with Lung Cancer for Treatment with EGFR and ALK Tyrosine Kinase Inhibitors Summary of Recommendations Section I. When Should Molecular Testing of Lung Cancers Be Performed?
Question 1. Which Patients Should Be Tested for EGFR Mutations and ALK Rearrangements? 1.1a: Recommendation: EGFR molecular testing should be used to select patients for EGFR targeted tyrosine kinase inhibitor therapy, and patients with lung adenocarcinoma should not be excluded from testing on the basis of clinical characteristics. 1.1b: Recommendation: ALK molecular testing should be used to select patients for ALK targeted tyrosine kinase inhibitor therapy, and patients with lung adenocarcinoma should not be excluded from testing on the basis of clinical characteristics. 1.2: Recommendation: In the setting of lung cancer resection specimens, EGFR and ALK testing is recommended for adenocarcinomas and mixed lung cancers with an adenocarcinoma component, regardless of histologic grade. In the setting of fully excised lung cancer specimens, EGFR and ALK testing is not recommended in lung cancers that lack any adenocarcinoma component, such as “pure” squamous cell carcinomas, “pure” small cell carcinomas, or large cell carcinomas lacking any immunohistochemistry (IHC) evidence of adenocarcinoma differentiation. 1.3: Recommendation: In the setting of more limited lung cancer specimens (biopsies, cytology) where an adenocarcinoma component cannot be completely excluded, EGFR and ALK testing may be performed in cases showing squamous or small cell histology but clinical criteria (eg, young age, lack of smoking history) may be useful in selecting a subset of these samples for testing. 1.4: Recommendation: To determine EGFR and ALK status for initial treatment selection, primary tumors or metastatic lesions are equally suitable for testing. 1.5: Expert consensus opinion: For patients with multiple, apparently separate, primary lung adenocarcinomas, each tumor may be tested but testing of multiple different areas within a single tumor is not necessary. Question 2. When Should a Patient Specimen Be Tested for EGFR Mutation or ALK Rearrangement? 2.1a: Recommendation: EGFR mutation testing should be ordered at the time of diagnosis for patients presenting with advanced-stage disease (stage IV according to the 7th edition TNM staging system) who are suitable for therapy or at time of recurrence or progression in patients who originally presented with lower-stage disease but were not previously tested. 2.1b: Suggestion: ALK rearrangement testing should be ordered at the time of diagnosis for patients presenting with advanced-stage disease (stage IV according to the 7th edition TNM staging system) who are suitable for therapy or at time of recurrence or progression in patients who originally presented with lower-stage disease but were not previously tested. 2.2a: Expert consensus opinion: EGFR testing of tumors at diagnosis from patients presenting with stage I, II, or III disease is encouraged but the decision to do so should be made locally by each laboratory, in collaboration with its oncology team. 2.2b: Expert consensus opinion: ALK testing of tumors at diagnosis from patients presenting with stage I, II, or III disease is encouraged, but the decision to do so should be made locally by each laboratory, in collaboration with its oncology team. 2.3: Recommendation: Tissue should be prioritized for EGFR and ALK testing. Question 3. How Rapidly Should Test Results Be Available? 3.1: Expert consensus opinion: EGFR and ALK results should be available within 2 weeks (10 working days) of receiving the specimen in the testing laboratory.