Comparative analysis of epidermal growth factor receptor mutations and gene amplification as predictors of gefitinib efficacy in Japanese patients with nonsmall cell lung cancer.

Background: Because the investigation of epidermal growth factor receptor gene (EGFR) status as a predictor of gefitinib efficacy in Japanese patients has shown promise, the authors evaluated EGFR mutations and gene amplification in biopsy specimens from Japanese patients with nonsmall cell lung cancer (NSCLC) who received treatment with gefitinib to analyze the correlation between EGFR gene status and clinical outcome.

Methods: Fifty-nine patients were enrolled in this study. EGFR gene amplification was evaluated by fluorescence in situ hybridization (FISH), and EGFR mutations in exons 18, 19, and 21 were analyzed by polymerase chain reaction and direct sequencing.

Results: EGFR mutations were detected in 17 patients (28.8%). FISH-positive results were observed in 26 patients (48.1%). The response rate was significantly higher in the patients with EGFR mutations than in the patients without mutations (58.8% vs 14.3%; P=.0005). No significant difference in the response rate was observed between FISH-positive patients and FISH-negative patients (31.8% vs 21.4%; P=.4339). EGFR mutation was correlated with both a longer time to progression (TTP) (7.3 months vs 1.8 months; P=.0030) and longer overall survival (OS) (18.9 months vs 6.4 months; P=.0092). No significant differences in TTP or OS were observed between FISH-positive patients andFISH-negative patients. The results from a multivariate analysis indicated that EGFR mutations maintained a significant association with longer TTP and longer OS.

Conclusions: The results of this study suggested that EGFR mutations may serve as predictors of response and survival and that the role of EGFR gene amplification is not a predictor of gefitinib efficacy in Japanese patients with NSCLC.