Reflex Testing for Epidermal Growth Factor Receptor Mutation and Anaplastic Lymphoma Kinase Fluorescence In Situ Hybridization in Non–Small Cell Lung Cancer

Abstract

Abstract Context.—Non–small cell lung cancer (NSCLC) is a poor-prognosis malignancy for which more effective treatments are needed, with accumulating clinical experiences supporting benefits of receptor tyrosine kinase inhibitors for patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. Objective.—To review completed and ongoing clinical trials of EGFR tyrosine kinase inhibitors for EGFR mutation–positive NSCLC and an ALK inhibitor for those with ALK rearrangement, while also exploring practical issues surrounding the implementation of molecular testing as a routine component of the diagnostic workup of NSCLC in the United States. Data Sources.—Published biomedical literature, abstracts presented at recent major oncology meetings, and ClinicalTrials.gov. Conclusions.—Continually evolving evidence indicates the possible efficacy of molecularly targeted agents for the treatment of advanced NSCLC, especially adenocarcinoma. To identify patients who will most likely benefit from the targeted therapy, routine determination of the corresponding genetic alterations after histologic diagnosis of NSCLC (reflex molecular testing for EGFR mutations and ALK rearrangement) should be considered.