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| 1 | 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显示文摘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。 | 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) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | Human apolipoprotein A-gene expression increase high-density lipoprotein and suppresses atherosclerosis in the apoprotein E-deficientmouse 显示文摘 | Plump A S Scott C J Breslow J L | 1994 | Proc Natal Acad Sci USA1994，91，： | 2 |
| 3 | Species diversity enhance ecosystem functioning through inter- specific facilitation显示文摘 | BREDLEY J C MARGARET A P SCOTT L C | 2002 | Nature2002，24，： | 1 |
| 4 | Gold and trace element zonation in pyrite using a laser imaging technique: Implications for the timing of gold in orogenic and Carlin- style sediment- hosted deposits 显示文摘 | R R Large L Danyushevsky C Hollit V Maslennikov S Meffer S Gilbert S Bull R Scott P Emsbo H Thomas B Singh J Foster | 2009 | Economic Geology2009，104，5： | 1 |
| 5 | LAMP proteins are required for fusion of lysosomes with phagosomes显示文摘 | Huynh K K Eskelinen E L Scott C C | 2007 | EMBO J2007，26，： | 1 |
| 6 | Ferroelectric thin films in integrated microelectronic devices 显示文摘 | Scott J F Paz de Araujo C A McMillan L D | 1992 | Ferroelectrics1992，133，： | 1 |
| 7 | Development of coarsegrained facies in lacustrine rift basins, example from East of America 显示文摘 | Scholz C A Rosendahl B R Scott D L | 1990 | Geology1990，18，2： | 1 |
| 8 | Validation of the RTOG recursive partitioning analysis (RPA) classifica- tion for brain metastases显示文摘 | Gaspar L E Scott C Murray K | 2000 | Int J Radiat Oncol Biol Phys2000，47，4： | 1 |
| 9 | Validation of real-time three-dimensional echocardiography for quantifying left ventricular volumes in the presence of a left ventricular aneurysm: in vitro and in vivo studies显示文摘 | Jian Xin Qin Michael Jones Takahiro Shiota Neil L Greenberg Hiroyuki Tsujino Michael S Firstenberg Pankaj C Gupta Arthur D Zetts Yong Xu Jing Ping Sun Lisa A Cardon Jill A Odabashian Scott D Flamm Richard D White Julio A Panza James D Thomas | 2000 | Journal of the American College of Cardiology2000，，3： | 1 |
| 10 | Treatment with interferon-a2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques 显示文摘 | Falzarano D de Wit E Rasmussen AL Feldmann F Oku- mura A Scott DP Brining D Bushmaker T Martellaro C Baseler L Benecke AG Katze MG Munster VJ Feldma- nn H | 2013 | Nat Med2013，19，10： | 1 |
| 11 | Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases:final report of RTOG protocol 90-05显示文摘 | Shaw E Scott C Souhami L | 2000 | Int J Radiat Oncol Biol Phys2000，47，2： | 1 |
| 12 | Recursive partitioning analysis(RPA) of prognostic factors in three Radiation Therapy Oncology Group(RTOG) brain metastases trials显示文摘 | GASPAR L SCOTT C ROTMAN M | 1997 | Int J Radiat Oncol Biol Phys1997，37，4： | 1 |
| 13 | Fatigue-free ferroelectric capacitors with platinum electrodes 显示文摘 | ARAUJO C A CUCHIARO J D MCMILLAN L D SCOTT M C SCOTT J F | 1995 | Nature (London)1995，374，： | 1 |
| 14 | Dual-action penems and carbapenems显示文摘 | Alfred J C Scott L D Norma K D | 1992 | J Med Chem1992，35，10： | 1 |
| 15 | Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials显示文摘 | Gaspar L Scott C Rotmann M | 1997 | Int J Radiat Oncol Biol Phys1997，37，4： | 1 |
| 16 | Enterprise and inequality:a study of Avon in South Africa显示文摘 | SCOTT L DOLAN C JOHNSTONE-LOUIS M | 2012 | Entrepreneurship Theory and Practice2012，36，3： | 1 |
| 17 | Cleaning up clostridium difficile infection显示文摘 | Matthew R T Scott C L Douglas R | 2002 | Mayo Clin Proc2002，76，9： | 1 |
| 18 | A proposed eye irritation testingstrategy to reduce and replace in vivo studies using Bottom-Up andTop-Down approaches显示文摘 | Scott L Eskes C Hoffmann S | 2010 | Toxicology in Vitro2010，24，1： | 1 |
| 19 | An algorithm for associating the features of two patterns显示文摘 | G L Scott H C Longuet-Higgins | 1991 | Proc Royal Society London1991，224，： | 1 |
| 20 | The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer 显示文摘 | Scott H R McMillan D C Forrest L M | 2002 | BrJ Cancer2002，87，3： | 1 |
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