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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 | Drought is normal: the socio-technical evolution of drought and water demand in England and Wales, 1893-2006 显示文摘 | Vanessa T Heather C Will M | 2009 | Journal of Historical Geography2009，35，3： | 1 |
| 3 | Fatty acid transporterlevels and palmitate oxidation rate correlate with ejection fraction inthe infarcted rat heart显示文摘 | Heather L C Cole M A Lygate C A | 2006 | Cardiovasc Res2006，72，3： | 1 |
| 4 | Rethinking Individualism and Col- lectivism: Evaluation of Theoretical Assumptions and Meta- Analyses 显示文摘 | OYSERMAN D HEATHER M C KEM- MELMEIR M | 2002 | Psychological Bulletin2002，128，1： | 1 |
| 5 | Assessing the work environment for creativity显示文摘 | Amabile T M Regina C Heather C | 1996 | Academy of Management Journal1996，39，5： | 1 |
| 6 | Assessing the work environment for creativity显示文摘 | Amabile T M Regina C Heather C | 1996 | Journa1996，39，5： | 1 |
| 7 | Minocyclinetherapy for traumatic ound infections caused by the multidrug-resistant Acinetobacter baumanni-Acinetobacter calcoaceticus complex显示文摘 | Matthew E Griffith M D Heather C | 2008 | Infect Dis Clin Pract2008，16，1： | 1 |
| 8 | Photocatalytic degradation of 17 - β- oestradiol on immobilized TiO2 显示文摘 | Heather M C Brian R E J Anthony Byrne | 2000 | Applied Catalysis B : Environmental2000，24，1： | 1 |
| 9 | Vibrational spectroscopic characterizationof hematite,maghemite,and magnetite thin films produced by vapordeposition显示文摘 | Aaron M J Heather C A | 2010 | Applied Materials&Interfaces2010，2，10： | 1 |
| 10 | Dipro-tected Triflylguanidines:? A New Class of Guanidinylation Reagents 显示文摘 | Feichtinger K Heather C Z Sings L Goodman M | 1998 | J Org Chem1998，63，： | 1 |
| 11 | Assessing the Work Environment for Creativity 显示文摘 | Amabile T M Regina C Heather C Jeffrey L Michael H | 1996 | Academy of Management Journal1996，39，5： | 1 |
| 12 | Kisspeptin neurons as central processors in the regulation of gonadotro-pin-releasing hormone secretion显示文摘 | Heather M D Donald K C Robert A S | 2006 | Endocrinology2006，147，3： | 1 |
| 13 | On the existence of FNs, a theoretical and experimental study显示文摘 | Heather M N Mark S G Karl C | 2003 | Journal of the Physical Chemistry A2003，107，34： | 1 |
| 14 | Hard metal disease 显示文摘 | Bech A O Kipling M D Heather J C | 1962 | Br J Ind Med1962，19，4： | 1 |
| 15 | A Common Network of Functional Areas for Attention and Eye Movements显示文摘 | Maurizio Corbetta Erbil Akbudak Thomas E Conturo Abraham Z Snyder John M Ollinger Heather A Drury Martin R Linenweber Steven E Petersen Marcus E Raichle David C Van Essen Gordon L Shulman | 1998 | Neuron1998，，4： | 1 |
| 16 | Assessing the Work En-vironment for Creativity显示文摘 | Amabile T M Regina C Heather C | 1996 | Academy ofManagement Journal1996，39，5： | 1 |
| 17 | Treatment Options for the menopausal Woman显示文摘 | Madelon LF Maurice C Heather M | 2001 | Spine2001，26，2： | 1 |
| 18 | Kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion 显示文摘 | HEATHER M D DONALD K C ROBERT A S | 2006 | Endocrinology2006，147，3： | 1 |
| 19 | Mutations perturbing petal cell shape and anthoeyanin synthe sis influence bumblebee perception of Antirrhinum majus flower colour显示文摘 | ADRIAN G D HEATHER M W SARAH E J BEVERLEY J G LARS C | 2007 | Arthropod-Plant Interactions2007，1，1： | 1 |
| 20 | The Debt Maturity Structure of Small Firms显示文摘 | SCHERR FREDERICK C HULBURT HEATHER M | 2001 | Financial Management2001，，： | 1 |
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