Effects of p450 Polymorphisms on the Clinical Outcomes of Gefitinib Treatment in Patients with Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer

Genet Test Mol Biomarkers. 2022 Dec;26(12):582-588. doi: 10.1089/gtmb.2022.0070.

Abstract

Aims: In this study, we determined whether different genotypes of drug-metabolizing enzymes are associated with the therapeutic effects of gefitinib in non-small cell lung cancer (NSCLC). Methods: A retrospective analysis of 112 patients with stage III or IV NSCLC was performed. The clinical characteristics of these patients, including progression-free survival (PFS), outcome of gefitinib treatment, and relationship between the genotypes of rs1065852/rs2242480 and prognosis, were analyzed. Results: The rs1065852 CT/TT genotype was associated with worse prognosis than the CC type (p = 0.0306), and the median PFS was lower than that with the CC type (287 days vs. 350 days). Compared with those with CC+CC genotypes, individuals carrying T alleles (CT/TT+CT/TT) at rs1065852/rs2242480 had a poorer prognosis, and the median PFS of CT/TT+CT/TT at rs1065852/rs2242480 was significantly lower than that of the CC+CC type (188 days vs. 444.5 days). Conclusions: Genotypes of the drug-metabolizing enzymes rs1065852 and rs2242480 have an impact on the prognosis of patients with NSCLC treated with gefitinib.

Keywords: CYP2D6; CYP3A4; gefitinib; non-small cell lung cancer; single nucleotide polymorphisms.

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cytochrome P-450 Enzyme System / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / therapeutic use
  • Gefitinib / therapeutic use
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies

Substances

  • Gefitinib
  • Cytochrome P-450 Enzyme System
  • ErbB Receptors
  • Antineoplastic Agents
  • Protein Kinase Inhibitors