Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Clin Lung Cancer. 2011 Jan;12(1):56-61. doi: 10.3816/CLC.2011.n.008.
The aim of this study was to analyze the factors independent of epidermal growth factor (EGFR) gene mutations that affect the progression-free survival (PFS) of patients with advanced non-small-cell lung cancer (NSCLC) after gefitinib therapy.
Eighty patients with advanced NSCLC between January 2003 and April 2010 at Kyoto University Hospital were analyzed for EGFR somatic mutations and treated with gefitinib. We adopted the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method for determination of EGFR mutation status. To evaluate risk factors associated with PFS, Cox proportional hazards regression model with a step-down procedure was used. Proportional hazards assumptions were checked and satisfied; only those variables with statistically significant results in univariate analysis were included in a multivariate analysis.
The median PFS of patients with EGFR mutations were significantly longer than in patients with wild-type EGFR. The median PFS of patients after first-line gefitinib therapy was significantly longer than those who received treatment as a second-line therapy. The median PFS of patients over 75 years of age was significantly longer than in younger patients. Based on multivariate analysis, wild-type EGFR status and age < 75 years were significant and independent negative factors that affect PFS after gefitinib therapy.
In this study, we showed the EGFR mutants and age > 75 years were good predictive factors for PFS after gefitinib therapy, suggesting that first-line gefitinib treatment for older patients is efficacious regardless of EGFR mutational status.
本研究旨在分析除表皮生长因子(EGFR)基因突变以外影响吉非替尼治疗后晚期非小细胞肺癌(NSCLC)患者无进展生存期(PFS)的独立因素。
京都大学医院 2003 年 1 月至 2010 年 4 月期间收治的 80 例晚期 NSCLC 患者进行了 EGFR 体细胞突变分析,并接受吉非替尼治疗。我们采用肽核酸锁核酸聚合酶链反应夹心法检测 EGFR 突变状态。为评估与 PFS 相关的风险因素,采用逐步下行的 Cox 比例风险回归模型进行分析。检查并满足比例风险假设;仅将单变量分析中具有统计学意义的变量纳入多变量分析。
有 EGFR 突变的患者的中位 PFS 明显长于 EGFR 野生型患者。一线吉非替尼治疗的患者中位 PFS 明显长于二线治疗的患者。75 岁以上患者的中位 PFS 明显长于较年轻患者。多变量分析显示,EGFR 野生型状态和年龄<75 岁是影响吉非替尼治疗后 PFS 的显著和独立的负面因素。
在这项研究中,我们表明 EGFR 突变和年龄>75 岁是吉非替尼治疗后 PFS 的良好预测因素,提示一线吉非替尼治疗对于老年患者无论 EGFR 突变状态如何均有效。