EML4-ALK Rearrangement and Its Clinical Significance in Chinese Patients with Advanced Non-Small Cell Lung Cancer

Abstract

Objective: To identify the clinicopathological characteristics and clinical outcomes of Chinese patients with non-small cell lung cancer (NSCLC) and to investigate possible associations of NSCLC with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. Methods: Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at the Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization and confirmed by immunohistochemistry. EGFR mutations were determined using denaturing high-performance liquid chromatography. Results: The incidence of EML4-ALK was 9.7% (11/113). Patients with EML4-ALK were more likely to present the EGFR wild type (WT; p = 0.033). Response to EGFR-tyrosine kinase inhibitor (TKI) was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3 vs. 46.9%, p = 0.451), but progression-free survival (PFS) was inferior compared to those with EGFR mutation (2.1 vs. 8.8 months, p = 0.032), and similar to patients with WT/nonrearrangement (2.1 vs. 2.2 months, p = 0.696; and general p = 0.023 between the three cohorts). Moreover, 2 patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared to patients with single EML4-ALK rearrangement. Conclusions: Patients with EML4-ALK conferred similar objective response rates after EGFR-TKI although inferior PFS compared to those with EGFR mutation. Coexistence of EML4-ALK and EGFR mutation might represent a separate NSCLC genotype.