帕博利珠单抗联合以铂类为基础的化疗治疗非小细胞肺癌合并稳定性脑转移患者的结局:KEYNOTE-021、-189和-407研究的汇总分析  

Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases:Pooled Analysis of KEYNOTE-021,-189,and-407

作　　者：周清(翻译校对)[1] Steven F Powell Delvys Rodríguez-Abreu Corey J Langer Ali Tafreshi Luis Paz-Ares Hans-Georg Kopp Jeronimo Rodríguez-Cid Dariusz M Kowalski Ying Cheng Takayasu Kurata Mark M Awad Jinaxin Lin Bin Zhao M Catherine Pietanza Bilal Piperdi Marina C Garassino Steven F Powell;Delvys Rodríguez-Abreu;Corey J Langer;Ali Tafreshi;Luis Paz-Ares;Hans-Georg Kopp;Jeronimo Rodríguez-Cid;Dariusz M Kowalski;Ying Cheng;Takayasu Kurata;Mark M Awad;Jinaxin Lin;Bin Zhao;M Catherine Pietanza;Bilal Piperdi;Marina C Garassino(Sanford Health,Sioux Falls,South Dakota;Complejo Hospitalario Universitario Insular-Materno Infantil,Universidad de Las Palmas de Gran Canaria,Gran Canaria,Spainospital Universitario Insular de Gran Canaria,Las Palmas de Gran Canaria,Las Palmas de Gran Canaria,Spain;Abramson Cancer Center,University of Pennsylvania,ladelphia,Pennsylvania;Wollongong Private Hospital,University of Wollongong,Wollongong,Australia;Hospital Universitario 12 de Octubre,CNIO,Universidad Complutense and Ciberonc,Madrid,Spain;Robert Bosch Centrum für Tumorerkrankungen,Robert Bosch Cancer Center,Klinik Schillerhohe,Gerlingen,Germany;Oncology Center,Médica Sur Hospital-Instituto Nacional de Enfermedades Respiratorias,Mexico City,Mexico;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Poland;Jilin Cancer Hospital,Changchun,Jilin,People's Republic of China;Department of Thoracic Oncology,Kansai Medical University Hospital,Hirakata,Osaka,Japan;Massachusetts General Hospital Cancer Center and Harvard Medical School,Boston,Massachusetts;Merck Sharp&Dohme Corp.,a subsidiary of Merck&Co.,Inc.,Kenilworth,New Jersey;Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori,Milan,Italy)

机构地区：[1]广东省人民医院肺三科广东省医学科学院广东省肺癌研究所,广州510080 [2]Sanford Health,Sioux Falls,South Dakota [3]Complejo Hospitalario Universitario Insular-Materno Infantil,Universidad de Las Palmas de Gran Canaria,Gran Canaria,Spainospital Universitario Insular de Gran Canaria,Las Palmas de Gran Canaria,Las Palmas de Gran Canaria,Spain [4]Abramson Cancer Center,University of Pennsylvania,ladelphia,Pennsylvania [5]Wollongong Private Hospital,University of Wollongong,Wollongong,Australia [6]Hospital Universitario 12 de Octubre,CNIO,Universidad Complutense and Ciberonc,Madrid,Spain [7]Robert Bosch Centrum für Tumorerkrankungen,Robert Bosch Cancer Center,Klinik Schillerhohe,Gerlingen,Germany [8]Oncology Center,Médica Sur Hospital-Instituto Nacional de Enfermedades Respiratorias,Mexico City,Mexico [9]Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Poland [10]Jilin Cancer Hospital,Changchun,Jilin,People's Republic of China [11]Department of Thoracic Oncology,Kansai Medical University Hospital,Hirakata,Osaka,Japan [12]Massachusetts General Hospital Cancer Center and Harvard Medical School,Boston,Massachusetts [13]Merck Sharp&Dohme Corp.,a subsidiary of Merck&Co.,Inc.,Kenilworth,New Jersey [14]Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori,Milan,Italy

出　　处：《中国肺癌杂志》2022年第1期I0007-I0018,共12页Chinese Journal of Lung Cancer

摘　　要：背景与目的此项探索性分析回顾评价了晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的结局,旨在确定基线时合并脑转移是否会影响一线应用帕博利珠单抗联合化疗(pembrolizumab plus chemotherapy,PC)比对单用化疗的疗效。患者和方法对KEYNOTE-021队列G(非鳞癌)、KEYNOTE-189(非鳞癌)和KEYNOTE-407(鳞癌)三项研究晚期NSCLC患者的数据进行汇总分析。患者接受含铂两药化疗和/或35个周期帕博利珠单抗治疗(每3周200 mg)。所有研究均纳入了经治或初治的稳定性脑转移患者(KEYNOTE-189与KEYNOTE-407研究纳入初治脑转移患者)。经治的脑转移患者已处于病情稳定的状态≥2周(KEYNOTE-021队列G患者≥4周),无新发或脑转移病灶扩大的证据且入组前至少3天以上未使用激素。初治的无症状脑转移患者需定期接受脑部影像学检查。结果共纳入1298例患者,其中171例有基线脑转移,1127例无脑转移。两组的中位随访时间(范围)在数据截止时分别为10.9(0.1-35.1)个月和11.0(0.1-34.9)个月。合并脑转移和无脑转移患者的总生存期[0.48(95%CI:0.32-0.70)和0.63(95%CI:0.53-0.75)]和无进展生存期[0.44(95%CI:0.31-0.62)和0.55(95%CI:0.48-0.63)]的风险比(PC/化疗)相似。合并脑转移的患者中,PC组和单用化疗组患者的中位总生存期分别为18.8个月和7.6个月,中位无进展生存期分别为6.9个月和4.1个月。无论是否合并脑转移,PC组患者的客观缓解率都高于单用化疗组,且缓解持续时间有显著延长。合并脑转移的患者中,PC组与单用化疗组的治疗相关不良事件发生率分别为88.2%和82.8%;而无脑转移的患者中,两组治疗相关不良事件的发生率分别为94.5%和90.6%。结论无论是否合并脑转移,与单用化疗相比,帕博利珠单抗联合以铂类为基础的组织学特异性化疗可改善所有PD-L1亚组的临床结局,其中包括PD-L1肿瘤比例评分<1%的患者,并且在晚期NSCLC患者中安全性良

关 键 词：帕博利珠单抗 脑转移 化疗 非小细胞肺癌 PD-L1 

分 类 号：R734.2[医药卫生—肿瘤]