biostudies-literatureSung JYKorea Institute of Oriental MedicineNational Research Foundation of Korea2109https://www.ebi.ac.uk/biostudies/studies/S-EPMC9495802biostudies-literatureUnknown10(9)This study aimed to determine the association between TMB and treatment outcomes in patients with epidermal growth factor receptor (EGFR)-mutated lung cancer that were treated with tyrosine kinase inhibitors (TKIs). The TMB was assessed using a 409-gene targeted next-generation sequencing panel. We compared the response rate (RR), progression-free survival (PFS), overall survival (OS), and frequency of secondary T790M mutations among the different TMB groups. The median TMB of the study population (n = 88) was 3.36/megabases. We divided 52 (59%) and 36 (41%) patients into the low and high TMB groups, respectively. A high TMB level was significantly associated with liver metastasis and more advanced stage (all <i>p</i> &lt; 0.05). RR was significantly lower in the high TMB group than that of the low TMB group (50.0% vs. 80.7%, all <i>p</i> = 0.0384). In multivariate analysis, high TMB was independently associated with a shorter PFS (hazard ratio [HR] = 1.80, <i>p</i> = 0.0427) and shorter OS (HR = 2.05, <i>p</i> = 0.0397) than that of the low TMB group. Further, high TMB was independently associated with decreased T790M mutation development. These results suggest that high TMB may be a predictive biomarker for adverse treatment outcomes and represent a patients' subgroup warranting tailored therapeutic approaches.BiomedicinesHigh Tumor Mutation Burden Is Associated with Poor Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.PMC9495802KSN20222402019R1F1A1041812Lee SHPark DWSung JYfalseHigh Tumor Mutation Burden Is Associated with Poor Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.This study aimed to determine the association between TMB and treatment outcomes in patients with epidermal growth factor receptor (EGFR)-mutated lung cancer that were treated with tyrosine kinase inhibitors (TKIs). The TMB was assessed using a 409-gene targeted next-generation sequencing panel. We compared the response rate (RR), progression-free survival (PFS), overall survival (OS), and frequency of secondary T790M mutations among the different TMB groups. The median TMB of the study population (n = 88) was 3.36/megabases. We divided 52 (59%) and 36 (41%) patients into the low and high TMB groups, respectively. A high TMB level was significantly associated with liver metastasis and more advanced stage (all <i>p</i> &lt; 0.05). RR was significantly lower in the high TMB group than that of the low TMB group (50.0% vs. 80.7%, all <i>p</i> = 0.0384). In multivariate analysis, high TMB was independently associated with a shorter PFS (hazard ratio [HR] = 1.80, <i>p</i> = 0.0427) and shorter OS (HR = 2.05, <i>p</i> = 0.0397) than that of the low TMB group. Further, high TMB was independently associated with decreased T790M mutation development. These results suggest that high TMB may be a predictive biomarker for adverse treatment outcomes and represent a patients' subgroup warranting tailored therapeutic approaches.2022-01-01T00:00:00Z2022 Aug2025-04-21T16:09:32.502Z2025-02-19T00:42:14.006ZS-EPMC94958023614021010.3390/biomedicines10092109