吉非替尼与化疗用于晚期非小细胞肺癌维持治疗疗效的临床观察

Clinical observation on EGFR-TKIs versus chemotherapy in maintenance therapy in advanced non-small cell lung cancer

目的表皮生长因子受体酪氨酸激酶抑制剂（Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors，EGFR-TKIs）吉非替尼及细胞毒化疗药物如吉西他滨、培美曲塞均是晚期非小细胞肺癌（Non-Small Cell Lung Canecer，NSCLC）维持治疗的有效手段，为对比两类药物维持治疗的临床疗效，我们进行了本项研究。方法回顾性分析接受吉非替尼、吉西他滨及培美曲塞维持治疗的65例晚期NSCLC，按照所接受的维持治疗方案种类分为吉非替尼维持治疗组和化疗维持治疗组，分析两组间疾病控制率、无进展生存（Progression-Free Survival，PFS）及总生存（Overall Survival，OS）的差异。结果65例患者34例为吉非替尼维持治疗（10例已知为EGFR基因突变患者），31例为化疗维持治疗（21例为吉西他滨维持化疗，10例为培美曲塞维持化疗），两种维持治疗方案获得的疾病控制率（70．6％比64．5％，P=0．791）、PFS（6．4月比5．0月，P=0．110）、OS（16．3月比12．0月，P=0．327）比较差异无统计学意义。分层分析发现EGFR突变状态未知时，吉非替尼对比吉两他滨、培美曲塞维持治疗PFS（4．0月比4．0月比5．0月，P=0．462）、OS（14．4月比12．0月比12．2月，P=0．540）比较差异无统计学意义，然而吉非替尼维持治疗组EGFR突变阳性患者较突变状态未知患者PFS（11．2月比4．0月，P=O．001）、OS（31．9月比14.4月，P=0．02）显著延长，差异有统计学意义。结论晚期NSCLC吉非替尼与化疗维持治疗疗效相似。吉非替尼维持治疗EGFR突变阳性患者较未知患者有明显获益，建议晚期NSCLC予吉非替尼维持治疗时常规行EGFR突变检测。

Objective EGFR-TKIs as gefitinib or cytotoxic chemotherapy drugs as gemcitabine and pemetrexed are all effective regimens in maintenance therapy in advanced NSCLC. In order to compare the clinical efficacy of these two maintenance therapy stategies, we carried out this research. Methods In our retrospective study, there were 65 advanced NSCLC patients received gefitinib, gemcitabine or pemetrexed maintenance therapy. These patients were divided into gefitinib or chemotherapy maintenance therapy groups. The difference such as disease control rate, PFS, and OS between the two groups were analyzed. Results 34 of 65 patients received gefitinib maintenance therapy （10 of 34 patients known as EGFR mutations）, and the other 31 patients received chemotherapy maintenance therapy （21 patients received gemcitabine maintenance therapy, 10 patients received pemetrexed maintenance therapy）. There were no statistically significant differences between gefitinib and chemotherapy maintenance therapy groups in disease control rate （70.6% vs.64.5%, P=0.791）, PFS （6.4 months vs.5.0 months, P=0.110）, and OS （16.3 months vs.12.0 months, P=0.327）. In stratified analysis, the PFS and OS were also not significantly different among gefitinb, gemcitabine, and pemetrexed maintenance therapy groups when EGFR mutation status was unknown （4.0 months vs.4.0 months vs.5.0 months, P=0.462） （14.4 months vs. 12.0 months vs. 12.2 months, P=0.540）. However, in gefitinb maintenance therapy group, the PFS and OS of EGFR mutation positive patients were significantly longer than those of the EGFR mutation unknown patients （11.2 months vs.4.0 months, P=0.001） （31.9 months vs.14.4 months, P=0.02）. Conclusions The efficacy was similar between gefitinib and chemotherapy maintenance therapy in advanced NSCLC. But there was more survival benefit in EGFR mutation patients than EGFR mutation unknown patients when gefitinib maintenance therapy was adopted, so, we suggested that EGFR mutation status should be routinely detected if gefitinib would be used in maintenance therapy in advanced NSCLC.