Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK

TLDR: EML4-ALK defines a molecular subset of NSCLC with distinct clinical characteristics and patients who harbor this mutation do not benefit from EGFR TKIs and should be directed to trials of ALK-targeted agents.

Abstract: Purpose The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of non–small-cell lung cancers (NSCLC). To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK. Patients and Methods Patients with NSCLC were selected for genetic screening on the basis of two or more of the following characteristics: female sex, Asian ethnicity, never/light smoking history, and adenocarcinoma histology. EML4-ALK was identified by using fluorescent in situ hybridization for ALK rearrangements and was confirmed by immunohistochemistry for ALK expression. EGFR and KRAS mutations were determined by DNA sequencing. Results Of 141 tumors screened, 19 (13%) were EML4-ALK mutant, 31 (22%) were EGFR mutant, and 91 (65%) were wild type (WT/WT) for both ALK and EGFR. Compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger (P < .001 and ...