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

Ji-Youn Sung1, Dong-Won Park2, Seung-Hyeun Lee3

  • 1Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Korea.

Biomedicines
|September 23, 2022
PubMed

Insights

High tumor mutational burden (TMB) in EGFR-mutated lung cancer patients treated with tyrosine kinase inhibitors (TKIs) is linked to poorer outcomes. High TMB predicts lower response rates, shorter progression-free survival, and overall survival.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Epidermal growth factor receptor (EGFR)-mutated lung cancer is a significant clinical challenge.
  • Tyrosine kinase inhibitors (TKIs) are standard treatments, but patient outcomes vary.
  • Tumor mutational burden (TMB) is an emerging biomarker in cancer research.

Purpose of the Study:

  • To investigate the association between TMB and treatment outcomes in EGFR-mutated lung cancer patients receiving TKIs.
  • To evaluate TMB as a predictive biomarker for response to TKI therapy.
  • To explore the relationship between TMB and survival in this patient cohort.

Main Methods:

  • A cohort of 88 patients with EGFR-mutated lung cancer treated with TKIs was analyzed.
  • Tumor mutational burden (TMB) was assessed using a 409-gene targeted next-generation sequencing panel.
  • Treatment outcomes including response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared between low and high TMB groups.

Main Results:

  • High TMB was associated with liver metastasis and advanced disease stage (p < 0.05).
  • Patients with high TMB exhibited significantly lower response rates (50.0% vs. 80.7%, p = 0.0384).
  • High TMB independently predicted shorter PFS (HR = 1.80, p = 0.0427) and OS (HR = 2.05, p = 0.0397), and decreased T790M mutation development.

Conclusions:

  • Elevated TMB may serve as a predictive biomarker for unfavorable treatment outcomes in EGFR-mutated lung cancer patients on TKIs.
  • A subgroup of patients with high TMB may benefit from tailored therapeutic strategies.
  • Further research is warranted to elucidate the mechanisms underlying TMB's impact on TKI efficacy.
Keywords:
epidermal growth factor receptorlung cancernext-generation sequencingsurvivaltargeted therapytumor mutation burden

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