帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析  

Pembrolizumab for Management of Patients with NSCLC and Brain Metastases:Long-term Results and Biomarker Analysis from A Non-randomised,Open-label,Phase 2 Trial

作　　者：Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对)[8] 

机构地区：[1]Department of Medicine(Medical Oncology),Yale School of Medicine,New Haven,CT,USA [2]Department of Pathology,Yale School of Medicine,New Haven,CT,USA [3]Department of Radiology,Yale School of Medicine,New Haven,CT,USA [4]Department of Neurosurgery,Yale School of Medicine,New Haven,CT,USA [5]Department of Therapeutic Radiology,Yale School of Medicine,New Haven,CT,USA [6]Interdepartmental Program in Computational Biology and Bioinformatics,Yale School of Medicine,New Haven,CT,USA [7]Department of Biostatistics,Yale School of Public Health,New Haven,CT,USA [8]华中科技大学同济医学院附属协和医院胸部肿瘤科

出　　处：《中国肺癌杂志》2021年第9期I0007-I0016,共10页Chinese Journal of Lung Cancer

基　　金：funded by Merck and the Yale Cancer Center;the Department of Defense through the Lung Cancer Research Program X81XWH-15-1-0203(S.Goldberg,PI)and W81XWH-16-1-0160(K.Schalper,PI);NIH grants Yale SPORE in Lung Cancer P50CA196530(R.Herbst,PI);R01 CA158167(H.Kluger and G.Desir Pis);K24CA172123(H.Kluger,PI);Yale SPORE in Skin Cancer P50 CA121974(M.Bosenberg and H.Kluger,Pis);R01 CA204002(L.Jilaveanu,PI);the Lung Cancer Research Foundation-LUNGevity and Melanoma Research Alliance,Award«308721(L.Jilaveanu,PI);Stand UpTo Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grants SU2C-AACR-DT17-15(P.Janne,A.Shaw,J.Wolchok,Pis);SU2C-AACR-DT22-17(L.Diaz,PI);the J.Aron Charitable Foundation(S.Goldberg).

摘　　要：背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。

关 键 词：非小细胞肺癌 脑转移 免疫治疗 帕博利珠单抗 

分 类 号：R734.2[医药卫生—肿瘤]