克唑替尼治疗晚期NSCLC患者单中心回顾性分析

Clinical Efficacy of Crizotinib in Treatment of Patients with Advanced NSCLC

背景与目的克唑替尼是针对间变淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因、ROS-1重排等靶点的药物。本文观察克唑替尼治疗ALK/ROS1重排阳性的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的近远期疗效。方法对2013年6月-2014年12月于北京肿瘤医院开始接受克唑替尼治疗的40例相应靶点阳性的NSCLC患者进行回顾性分析。结果本组40例,39例为腺癌或腺鳞癌,包括印戒细胞癌、腺泡型、乳头状腺癌等特点。中位年龄49.5岁,治疗总有效率62.5%,疾病控制率为95.0%。全组中位随访14.6个月,中位无进展生存时间(progression free survival,PFS)7.5个月,中位生存期(overall survival,OS)尚未到达,1年生存率77.4%。第一、二线较二线后治疗者中位PFS、OS有延长趋势,但无统计学意义(PFS:9 mo vs 6 mo,P=0.06;OS:21.5 mo vs 14.6 mo,P=0.12)。20例进展者以脑转移为进展部位。进展后接受二代/三代ALK-酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)的患者表现出疾病控制、生存延长的疗效。不良反应主要为消化道反应、转氨酶升高、特征性的视觉异常等。结论本组克唑替尼治疗相应靶点阳性晚期NSCLC临床特点、疗效及不良反应与国际报道相近。脑转移进展是克唑替尼治疗后进展的常见形式,克唑替尼耐药者给予二代/三代ALK-TKI可延迟进展。

Background and objective Crizotinib was developed in recent years based on targets of anaplastic lymphoma kinase（ALK） fusion genes. The aim of this study is to explore the efficacy of crizotinib in treatment of non-small cell lung cancer（NSCLC） with ALK/ROS1 rearrangement. Methods Retrospective analysis of 40 patients with ALK/ROS1-positive NSCLC, who received treatment in Beijing Cancer Hospital during the period from Jun. 2013 to Dec. 2014. Results Among these cases, 39 were adenocarcinoma and adenosquamous carcinoma, with characters involving signet-ring cell carcinoma, polypoid adenocarcinoma, acini and papillary adenocarcinoma. The median age was 49.5 years old, with the overall response rate of 62.5% and disease control rate of 95.0%. Of all the cases, median follow-up was 14.6 months and median PFS 7.5 months; median OS has not been reached; the one-year survival rate was 77.4%. The median PFS and OS of patients receiving first and second-line treatment tend to be longer than those who received post-second line treatment, but with no statistical significance（PFS： 9 mo vs 6 mo, P=0.06; OS： 21.5 mo vs 14.6 mo, P=0.12）. Twenty patients who experienced progression in brain metastases. After experiencing progression, the patients receiving 2nd/3rd generation ALK-TKI treatment showed efficacy of disease control and survival. The adverse events include gastrointestinal reaction, transaminase elevation, and distinctive visual abnormalities, etc. Conclusion The clinical features, efficacy, and adverse events of crizotinib in the treatment of the 40 patients with ALK/ROS1-positive NSCLC are similar to the data from the previous reports. The most common site of progression was brain metastases. The treatment of crizotinib-resistant patients using 2nd/3rd generation ALK-TKI could delay progression.