克唑替尼在ALK阳性晚期NSCLC患者中的疗效和安全性评价及其预后影响因素

Evaluation of efficacy and safety of crizotinib and its prognostic factors in patients with ALK-positive advanced non-small cell lung cancer

目的探讨克唑替尼在间变性淋巴瘤激酶（ALK）阳性晚期非小细胞肺癌（NSCLC）患者中的疗效和安全性，并重点分析其预后影响因素。方法收集2013年1月至2016年9月在北京协和医院就诊且经细胞学或组织学证实的晚期（ⅢB～Ⅳ期）ALK阳性NSCLC患者50例，记录相关临床信息、治疗方案并随访疗效和安全性，分析预后影响因素。结果截至随访结束，进展患者（24例）中位无进展生存期（PFS）为9.6个月（95%CI为8.3～10.9个月），其中5例死亡；未进展患者（26例）中位随访时间为10.7个月。最常见的不良反应为肝功能异常（48.0%，24/50）；在KaplanMeier单因素分析中，≤40岁的患者拥有更长的PFS（P=0.017），且COX回归多因素分析（Enter法）也有意义（HR=6.1，95%CI为1.4～27.5，P＝0.018）；而性别（HR=0.8，95%CI为0.2～2.6，P＝0.697）、吸烟史（HR=1.5，95%CI为0.4～5.6，P＝0.524）、病理类型（HR=1.1，95%CI为0.3～4.2，P＝0.922）、分期（HR=1.7，95%CI为0.4～8.4，P＝0.502）、表皮生长因子受体（EGFR）突变型（HR=0.4，95%CI为0.4～4.3，P＝0.461）、EGFR未知（HR=1.3，95%CI为0.3～6.1，P＝0.727）、美国东部肿瘤协作组体能状态评分（HR=2.0，95%CI为0.6～6.8，ECOG PS评分，P=0.290）、既往治疗情况（HR=0.6，95%CI为0.2～1.8，P=0.385）和脑转移情况（HR=0.7，95%CI为0.1～3.2，P=0.628）均与疾病进展时间无关。结论克唑替尼对晚期ALK阳性NSCLC患者有良好的疗效，安全可耐受，年龄是其预后的独立影响因素。

ObjectiveTo investigate the efficacy and safety of crizotinib in patients with advanced anaplastic lymphoma kinase （ALK）positive nonsmall cell lung cancer （NSCLC）, and focuse on analysis of its prognostic factors. MethodsFifty patients with advanced （stage ⅢBⅣ） ALKpositive NSCLC confirmed by cytology or histology in Peking Union Medical Collage Hospital from January 2013 to September 2016 were collected. The relevant clinical information and treatment protocols were recorded. The efficacy and safety of crizotinib were followed up, and its prognostic factors were analyzed. ResultsAt the end of followup, the median progression free survival （PFS） of progressed patients （n=24） was 9.6 months （95%CI： 8.310.9 months）, of which five patients died. The median followup time of nonprogressed patients （n=26） was 10.7 months. The most common adverse event was abnormal liver function （48.0%, 24/50）. In the single factor analysis of KaplanMeier, younger or equal to 40 years old patients had a longer PFS （P=0.017）, and the COX regression analysis （Enter method） also had statistical significance differences （HR=6.1, 95%CI： 1.427.5, P=0.018）. However, gender （HR=0.8, 95%CI： 0.22.6, P=0.697）, smoking history （HR=1.5, 95%CI： 0.45.6, P=0.524）, pathology （HR=1.1, 95%CI： 0.34.2, P=0.922）, tumor stage （HR=1.7, 95%CI： 0.48.4, P=0.502）, epidermal growth factor receptor （EGFR） mutant type （HR=0.4, 95%CI： 0.44.3, P=0.461）, EGFR unknown （HR=1.3, 95%CI： 0.36.1, P=0.727）, Eastern Cooperative Oncology Group Performance Status （ECOG） PS score （HR=2.0, 95%CI： 0.66.8, P=0.290）, the status of previous treatment （HR=0.6, 95%CI： 0.21.8, P=0.385） and brain metastasis （HR=0.7, 95%CI： 0.13.2, P=0.628） were not associated with disease progression. ConclusionCrizotinib has good efficacy and is safe and welltolerated to advanced ALKpositive NSCLC patients, and age is the independent prognostic factor.