Molecular determinants of clinical outcomes for anaplastic lymphoma kinase-positive non-small cell lung cancer in Chinese patients: A retrospective study

Abstract

Gene complexity affects the clinical outcomes of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we reviewed the medical records of patients with NSCLC between September 2015 and December 2020 in a single institution. We examined the clinical and genomic predictors of these outcomes using multivariate Cox proportional hazards analysis. Overall, 105 patients with ALK-rearranged NSCLC were included. Echinoderm microtubule-associated protein-like 4 (EML4) was the predominant fusion partner (96.2%). Five patients (4.8%) had non-EML4 fusion partners; three had novel partners. EML4::ALK variant 3 (36.5%) was predominant. One patient had the following three subtypes: E13::A20, E6ins33::A20, and E20::A20. Median progression-free survival (PFS), but not overall survival (OS), was significantly different between patients with variants 3 and 1. TP53 was the most common concomitant mutation (21.4%). The presence of TP53 mutations was associated with shorter PFS among patients who received ALK-TKI. Patients with concomitant oncogene mutations presented significantly shorter OS and PFS than those with only ALK rearrangement. In a multivariate Cox regression model, concomitant oncogene mutations and variant 3 carrier status were prognostic factors for PFS, whereas baseline brain metastasis was a prognostic factor for OS.

Keywords: Anaplastic lymphoma kinase; Brain metastasis; Concomitant mutations; TP53; Variant V3.