Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy

Oncol Res Treat. 2015;38(11):560-9. doi: 10.1159/000441367. Epub 2015 Oct 21.

Abstract

Background: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned.

Patients and methods: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR.

Results: Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC.

Conclusion: Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis / methods
  • ErbB Receptors / genetics*
  • Female
  • Gefitinib
  • Gene Expression Profiling / methods
  • Genetic Markers / genetics
  • Humans
  • Longitudinal Studies
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Prevalence
  • Quinazolines / therapeutic use*
  • Retrospective Studies
  • Risk Factors
  • Sex Distribution
  • Smoking / epidemiology
  • Switzerland / epidemiology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Genetic Markers
  • Quinazolines
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib