Mutation of the epidermal growth factor receptor gene and its impact on the efficacy of gefitinib in advanced non-small cell lung cance

Abstract

Mutations in the epidermal growth factor receptor (EGFR) gene are associated with subsets of non-small cell lung cancer (NSCLC). Some patients with EGFR mutations are responsive to targeted therapy with the EGFR tyrosine kinase inhibitor gefitinib. Here, the mutation status of EGFR was assessed in advanced-stage NSCLC patients to determine how mutation status influences the clinical efficacy of gefitinib. The study included 106 patients with advanced NSCLC who were treated with gefitinib. Exons 19 and 21 of EGFR were sequenced from tumor tissues samples by PCR, and patient clinical characteristics, short-term outcomes (partial response, stable disease, progressive disease), and survival [overall survival (OS) and progression-free survival (PFS)] were compared. EGFR mutations in either exon 19 or exon 21 were detected in 54.7% of cases. The EGFR gene mutation rate was significantly different in patients with different pathological types (χ(2)=6.612, P<0.05). The distribution of short-term outcomes differed significantly by EGFR gene mutation status, history of smoking, and bone metastasis (χ(2)=6.481~35.938, P<0.05). Further, OS and PFS was significantly higher following gefitinib in patients with EGFR mutations than those without EGFR mutation (χ(2)=19.135, 6.953, P<0.05). OS was also significantly higher in patients with an exon 19 deletion mutation than in those with the exon 21 point mutation (χ(2)=8.575, P<0.05). Cox multivariate regression analysis indicated that OS was correlated with the pathological type of the tumor (HR=4.877), US Eastern Cooperative Oncology Group Physical Status (ECOG PS) score (HR=3.087), and EGFR mutation status (HR=1.876) (all P<0.05), while PFS was correlated with ECOG PS score (HR=2.218), cycles of chemotherapy (HR=1.829), and EGFR mutation status (HR=1.840) (all P<0.05). Only mild adverse events were reported during gefitinib treatment. The findings indicate that gefitinib treatment can improve the clinical outcomes of NSCLC patients with EGFR mutation, prolonging their survival time with only mild adverse events.

Keywords: Non-small cell lung cancer; epidermal growth factor receptor; gefitinib; gene mutation; survival analysis.

Figures

Figure 1

Kaplan-Meier survival analysis for overall survival for NSCLC patients who were either positive or negative for EGFR mutation.

Figure 2

Kaplan-Meier survival analysis for progression-free survival of NSCLC patients who were positive or negative for EGFR mutation.

Figure 3

Kaplan-Meier survival analysis of overall survival of NSCLC patients with Exon 19 or Exon 21 EGFR mutation.

Figure 4

Kaplan-Meier survival analysis of progression-free survival for NSCLC patients with Exon 19 or Exon 21 mutation.