4.7 Article

High Tumor Mutation Burden Is Associated with Poor Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy

Journal

BIOMEDICINES
Volume 10, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines10092109

Keywords

lung cancer; next-generation sequencing; tumor mutation burden; survival; epidermal growth factor receptor; targeted therapy

Funding

  1. Korea Institute of Oriental Medicine of the Republic of Korea [KSN2022240]
  2. Basic Research Program through the National Research Foundation - Ministry of Science and ICT of the Republic of Korea [2019R1F1A1041812]
  3. National Research Council of Science & Technology (NST), Republic of Korea [KSN2022240] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
  4. National Research Foundation of Korea [2019R1F1A1041812] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study found that high TMB level is associated with adverse treatment outcomes in patients with EGFR-mutated lung cancer, suggesting that high TMB may serve as a predictive biomarker and require tailored therapeutic approaches.
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 p < 0.05). RR was significantly lower in the high TMB group than that of the low TMB group (50.0% vs. 80.7%, all p = 0.0384). In multivariate analysis, high TMB was independently associated with a shorter PFS (hazard ratio [HR] = 1.80, p = 0.0427) and shorter OS (HR = 2.05, p = 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.

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