Optimization of Patient Selection for Gefitinib in Non–Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation

摘要: Purpose: Mutations in epidermal growth factor receptor (EGFR) are strongly predictive of gefitinib efficacy non–small-cell lung cancer. However, the presence EGFR mutant nonresponses and nonmutant responses points out need for more comprehensive analysis. Patients Methods: For 69 cancer patients treated with gefitinib, we have extended our analysis to gene copy number by fluorescence situ hybridization, mutations K-ras, HER2, exon 20 direct sequencing, phosphatase tensin homologue expression immunohistochemistry, addition exons 18, 19, 21, phosphorylations Akt extracellular signal–regulated kinase reported previously. Results: mutation high were associated better objective response univariate analysis. only gefitinib-sensitive was independently both ( P = 0.011) survival 0.002) multivariate No K-ras mutation, including two mutants, showed response. In nonmutants, either or p-Akt overexpression exhibited poor time-to-progression whereas tended outcomes shorter 0.017). patient HER2 gefitinib. Reduced not sensitivity. Conclusion: Gefitinib-sensitive is single most important predictor sensitivity. phosphorylation aid prediction responsiveness