吉非替尼治疗化疗失败的局部晚期或转移性非小细胞肺癌疗效及生存的预测因素

Predictive factors of gefitinib response and survival in Chinese patients with local advanced or metastatic non-small cell lung cancer

背景与目的 吉非替尼是一种选择性表皮生长因子受体酪氨酸激酶抑制剂（EGFRTKI）,已被证实为治疗化疗失败的晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）患者的有效药物,其治疗亚洲晚期NSCLC患者的疗效与联合化疗的疗效相当。国外的临床研究结果显示,种族、性别、吸烟史及组织病理类型被认为是吉非替尼疗效及生存的相关因素。但在亚洲人群中,吉非替尼疗效及生存的预测因素尚未清楚。本研究回顾分析了中国153例局部晚期或转移性NSCLC患者的接受吉非替尼治疗的情况,旨在分析疗效与生存的预测因素。方法 对2003年11月至2004年6月,参加吉非替尼在中国的注册临床研究的153例NSCLC患者的临床、病理特征与疗效及生存的相关情况进行了回顾性分析。疗效相关性采用χ2检验及Logistic回归分析分别进行单因素及多因素分析;生存分析运用Logrank检验及Kaplan-Meier、Cox回归分析分别进行单因素及多因素分析。结果 153例可评价的患者中,多因素分析显示年龄≤65岁及从初诊到吉非替尼治疗的时间间隔≥6个月者,与客观有效率明显相关（P〈0.05）。中位随访时间10.0个月（0.5~16.8个月）,中位生存期为10.3个月（95%CI,8.1~12.6个月）,1年生存率为44.1%。COX回归分析显示,PS评分0-1、末次化疗达疾病控制以及吉非替尼治疗达疾病控制是生存的独立预后因素（P〈0.05）。结论 吉非替尼对既往化疗失败的局部晚期或转移性NSCLC的中国患者有较好的疗效。年龄≤65岁及从初诊到吉非替尼治疗的时间间隔为≥6个月是吉非替尼疗效的预测因素。PS评分0-1、末次化疗达疾病控制及吉非替尼治疗达疾病控制是生存的独立预后因素。

Background and objective Gefitinib, a selective inhibitor of epidermal growth factor receptor （EGFR） tyrosine kinase, has been approved effective in local advanced or metastatic non-small cell lung cancer （NSCLC）, with the equivalent response rate to that of chemotherapy in Asian patients. Asian ethnicity, gender, smoking history, adenocarcinoma histology were remarkably associated with gefitinib response and survival. However, predictive factors of gefitinib response and survival are still unclear in Asian population. In this study, we retrospectively reviewed the data of 153 Chinese NSCLC patients who received a single agent of gefitinib with the purpose of identifying the potential predictive factors of gefitinib response and survival. Methods Tumor response, survival and the clinicopathologie factors of 153 NSCLC patients treated between November of 2003 and June of 2004 were collected retrospectively from the multicenter clinical trial in China. Pearson Chi-square test and Logistic regression test were performed respectively as univariate and multivariate analyses of gefitinib response. Overall survivals between groups with different predictive factors were compared by log-rank tests. Multivariate analysis was performed to identify factors that independently predict for survival. Results A total of 153 patients were included in this analysis. Objective response rate was statistically significant higher in patients with younger age （≤65 years） and longer interval from diagnosis to gefitinib treatment （≥6 months） in multivariate analysis （P〈0.05）. The median follow-up duration was 10.0 months （0. 5-16.8）. The median survival was 10. 3 months （95% CI： 8. 1-12.6） and 1-year survival was 44.1%. Significant independent predictive factors associated with longer survival in multivariate analysis were good performance status （score 0-1）, controlled disease （CR＋PR＋SD） to most recent chemotherapy and controlled disease to gefitinib （P〈0. 05）. Conclusion Gefitinib is effective in local advanced or metastatic NSCLC patients who failed to chemotherapy in Chinese population. In Chinese NSCLC population, younger age （≤65 years） and longer interval from diagnosis to gefitinib treatment （≥6 months） were predictive factors in multivariate analysis for gefitinib response; good performance status （score 0-1）, controlled disease to most recent chemotherapy and controlled disease to gefitinib were independent prognostic factors for survival.