非小细胞肺癌患者外周血表皮生长因子受体T790M检测与奥希替尼疗效的相关性研究  

Epidermal Growth Factor Receptor T790M Detection in Predicting Efficacy of Osimertinib in Patients with Nonsmall Cell Lung Cancer

作　　者：龚磊[1,2] 潘志文 覃晶[1,2] 谢发君[1,2] 韩娜 卢红阳[1,2] GONG Lei;PAN Zhi-wen;QIN Jing;XIE Fa-jun;HAN Na;LU Hong-yang(Zhejiang Cancer Hospital,Hangzhou 310022,China;Zhejiang Key Laboratory of Diagnosis&Preatment Technology on Thoracic Oncology (Lung and Esophagus),Hcingzhou 310022,China)

机构地区：[1]浙江省肿瘤医院,浙江杭州310022 [2]浙江省胸部肿瘤(食管肺)诊治技术研究重点实验室,浙江杭州310022

出　　处：《中国肿瘤》2019年第3期234-239,共6页China Cancer

基　　金：浙江省医药卫生科技面上项目课题资助(2018KY313)

摘　　要：[目的]评估非小细胞肺癌患者第一代表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)获得性耐药后外周血EGFR T790M突变的阳性率和用外周血T790M检测结果预测奥希替尼疗效的可靠性。[方法]回顾性分析2017年3月至2018年6月经第一代EGFR-TKI治疗后获得性耐药且使用超级扩增阻滞突变系统(ultraamplification refractory mutation system,Ultra-ARMS)进行外周血EGFR T790M检测的原发性非小细胞肺癌患者。评估血T790M阳性患者使用奥希替尼的疗效。[结果]共有103例符合标准的第一代EGFR-TKI获得性耐药患者,其中28例(27.2%,28/103)血T790M阳性,75例(72.8%,75/103)血T790M阴性。血T790M阳性患者中,接受奥希替尼治疗有23例:部分缓解(partial response,PR) 15例,疾病稳定(stable disease,SD)6例,疾病进展(progression of disease,PD) 2例。疾病控制率(disease control rate,DCR) 91.3%,客观有效率(objective response rate,ORR)65.2%。奥希替尼治疗的中位无进展生存时间(progression free survival,PFS) 12.5个月(95%CI:11.2～13.8)。有9例血T790M阴性患者后续进行了组织检测,3例在组织中检测到T790M突变。有6例血T790M阴性的患者虽未再行组织检测,但要求试用奥希替尼靶向治疗,1例患者获得了PR,1例SD(PFS超过5个月)。[结论]对第一代EGFR-TKI获得性耐药后未能再次行组织活检的非小细胞肺癌患者,Ultra-ARMS方法检测血T790M阳性可预测奥希替尼疗效。血T790M检测阴性的患者建议再次取组织进行T790M检测以排除假阴性。组织检测是T790M检测的金标准,血T790M检测可作为补充。[Purpose] To detect epidermal growth factor receptor (EGFR) p.Thr790Met point mutation (T790M) in patients with non-small cell lung cancer (NSCLC) and to investigate the correlation between T790M detection and the efficacy of osimertinib.[Methods] One hundred and three NSCLC patients,who developed resistance to first generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) and admitted in Zhejiang Cancer Hospital from March 2017 to June 2018,were enrolled in the study. Plasma EGFR T790M was tested by ultra-amplification refractory mutation system (Ultra-ARMS). The efficacy of osimertinib in T790M-positive NSCLC patients was analyzed.[Results] Among 103 EGFR-TKI resistant NSCLC patients,plasma T790M was positive in 28 cases (27.2%) and negative in 75 cases (72.8%). In23 plasma T790M-positive patients receiving osimertinib treatment,there were partial response (PR) in15 cases,stable disease (SD) in 6 cases and progression of disease (PD) in 2 cases. The disease control rate (DCR) was 91.3%,and the objective response rate (ORR) was 65.2%. The median progression free survival (PFS) of osimertinib was 12.5 (95%CI:11.2~13.8) months. Nine plasma T790M-negative patients were subsequently examined with tissue specimens,and 3 of them were T790M-positive. Six plasma T790M-negative patients without tissue tests were treated with osimertinib,among whom 1achieved PR,and 1 achieved SD (PFS was longer than 5 months).[Conclusion] Plasma T790 M detection can predict the efficacy of osimeritinib in NSCLC patients with first-generation EGFR-TKI resistance. Patients with plasma negative T790 M are suggested to perform tissue T790 M test to exclude false negative results.

关 键 词：奥希替尼 表皮生长因子受体 酪氨酸激酶抑制剂 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]