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EGFR Polymorphism and Survival of NSCLC Patients Treated with TKIs: A Systematic Review and Meta-Analysis

Vladimir Jurisic1, Vladimir Vukovic2, Jasmina Obradovic3

  • 1Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.

Journal of Oncology
|April 8, 2020
PubMed

Insights

Epidermal growth factor receptor (EGFR) gene variations impact non-small-cell lung cancer (NSCLC) patient survival. Specific EGFR polymorphisms, like -216G>T and CA repeat, significantly affect outcomes in TKI-treated NSCLC patients.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Tyrosine kinase inhibitor (TKI) therapy has improved survival for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations.
  • The EGFR gene is highly polymorphic, with over 1200 known single nucleotide polymorphisms (SNPs).
  • The influence of EGFR polymorphisms on TKI treatment outcomes in NSCLC remains debated.

Purpose of the Study:

  • To quantitatively assess the association between ten specific EGFR SNPs and NSCLC patient survival.
  • To determine which EGFR polymorphisms significantly impact overall survival (OS) and progression-free survival (PFS) in NSCLC patients undergoing TKI therapy.

Main Methods:

  • A systematic literature review and meta-analysis were conducted following PRISMA guidelines.
  • Data were sourced from PubMed, Scopus, ISI Web of Science, and 14 GWAS electronic databases.
  • Pooled hazard ratios (HR) and 95% confidence intervals (CI) for OS and PFS were calculated using random or fixed effect models.

Main Results:

  • Out of ten investigated EGFR SNPs, only four (rs712829, rs11568315, rs2293347, rs4947492) showed a reported association with TKI treatment outcomes.
  • The rs712829 (-216G>T) polymorphism showed the longest median OS for homozygous wild genotype and shortest for variant allele carriers.
  • Meta-analysis confirmed that rs712829 (-216G>T) and rs11568315 (CA repeat) polymorphisms significantly affect OS and PFS in NSCLC patients treated with gefitinib or erlotinib.

Conclusions:

  • Specific EGFR polymorphisms, notably rs712829 (-216G>T) and the CA repeat polymorphism (rs11568315), significantly influence treatment outcomes in NSCLC patients receiving TKI therapy.
  • These findings highlight the potential role of pharmacogenomics in personalizing NSCLC treatment strategies.
  • Further research is warranted to fully elucidate the impact of EGFR genetic variations on TKI efficacy and patient prognosis.

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