Integrating POLE/POLD1 mutated for immunotherapy treatment planning of advanced stage non‐small cell lung cancer

Abstract

Abstract Background In this study, we evaluated the potential of DNA polymerase epsilon (POLE) and DNA polymerase delta 1 (POLD1) as prognostic biomarkers for immune checkpoint inhibitor (ICI) treatment in patients with advanced stage non‐small cell lung cancer (NSCLC). Methods Disease stage, PD‐L1 positivity, histological subtypes, POLE/POLD1 mutation status, tumor mutation burden (TMB), and response to ICIs in NSCLC cases were derived from AACR GENIE dataset (n = 24 120), TCGA‐Pan Lung Cancer dataset (n = 1144), AACR GENIE BPC NSCLC v2.0‐public (n = 2004), and Memorial Sloan Kettering‐Integrated Mutation Profiling of Actionable Cancer Targets dataset (n = 350). The smoking history from TCGA and AACR GENIE datasets was grouped into current, former or never‐smokers. Results POLE and POLD1 genetic alterations were identified in 5% and 2.6% of NSCLC patients, respectively. Current smokers had 9% and 4% of POLE/POLD1 mutations, respectively, versus 1.7% for both POLE and POLD1 mutations prevalence in never‐smokers. POLE/POLD1 mutations were associated with elevated mutation counts than those with wild‐type (median mutation counts 16 vs. 7, p 18 (p 18 can be a composite biomarker for selecting NSCLC patients with survival benefits to ICI treatment.

Keywords

• immunotherapy
• lung cancer
• POLE
• tumor mutation burden