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| 1 | 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研究的汇总分析显示文摘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患者中安全性良好。该方案是晚期NSCLC初治患者的标准方案,并可用于合并稳定性脑转移的患者。 | 周清(翻译校对) 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 | 2022 | 中国肺癌杂志2022，25，1： | 6 |
| 2 | Activation of silent replication origins at autonomously replicating sequence ele-ments near the HML locus in budding yeasi显示文摘 | VUJCIC M MILLER C A KOWALSKI D | 1999 | Molecular and Cellular Biology1999，19，9： | 1 |
| 3 | Self- compassion: A potential resource for young women athletes 显示文摘 | Mosewich A D Kowalski K C Sabiston C M | 2011 | Journalof Sport & Exercise Psychology2011，，33： | 1 |
| 4 | Use of Central Venous Catheter-Related Bloodstream Infection Prevention Pratices by US Hospital显示文摘 | Krein S L Hofer T P Kowalski C P | 2007 | Mayo Clin Proc2007，82，6： | 1 |
| 5 | Mycophenolic acid and Bregninar Inhibitors of Purine and Pyrimidne Synthesis Block the Glycosylation of Adhetion Molecules显示文摘 | ALLISON A C KOWALSKI W J MULLER C J | 1993 | Transplant Proc1993，25，2： | 1 |
| 6 | High performance liquid chromatography determination of sulphachloropyrazine residues in broiler and turkey edible tissues显示文摘 | KOWALSKI C J LEBKOWSKA-WIERUSZEWSKA B OSYPIUK M | 2009 | Journal of Chromatography B Analytical Technologies in the Biomedical Life Sciences2009，877，1819： | 1 |
| 7 | Cortactin regulates cell migration through activation of N-WASP显示文摘 | Kowalski JR Egile C Gil S | 2005 | J Cell Sci2005，118，1： | 1 |
| 8 | Epithelial salivary glands neoplasms in children and adolescents:a forty-four-year experience显示文摘 | Kowalski LP Saba LM | 2002 | Med Pediatr Oncol2002，39，6： | 1 |
| 9 | Response surface methodology: A restrospective and literature survey 显示文摘 | Myers R H Montgomery D C Vining G G Borror C M Kowalski S M | 2004 | Journal of Quality Technology2004，36，1： | 1 |
| 10 | Qualitative evaluation of alkali release during the pyrolysis of biomass显示文摘 | KOWALSKI T LUDWIG C WOKAUN A | 2007 | Energy Fuels2007，21，5： | 1 |
| 11 | The role of self - compassion in women' s self - determined motives to exercise and exercise - related outcomes 显示文摘 | Magnus C M R Kowalski K C McHugh T - L F | 2010 | Self and Identity2010，，09： | 1 |
| 12 | Associations between hospital and patient characteristics and breast cancer patients' satisfaction with nursing staff显示文摘 | Kowalski C Diener S E Steffen P | 2012 | Cancer Nursing2012，35，3： | 1 |
| 13 | Solving chemical problems with pattern recognition 显示文摘 | KOWALSKI B R BENDER C F | 1975 | NATURWISSEN- SCHAFTEN1975，62，： | 1 |
| 14 | Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management显示文摘 | Kowalski R Post D Schneider M C Britz J Thomas J Deierhoi M | 2003 | Clin Transplant2003，17，： | 1 |
| 15 | The relationship be- tween nurse practice environment, nurse work characteristics, burn- out and job outcome and quality of nursing care : a cross - sectional survey显示文摘 | Van Bogaert P Kowalski C Weeks SM | 2013 | Int J Nurs Stud2013，50，12： | 1 |
| 16 | Migration of central venous catheters: implications for initial catheter tip positinning显示文摘 | Kowalski C M Kaufman J A Rivitz S M | 1997 | J Vasc Interv Radiol1997，8，3： | 1 |
| 17 | The epidemiology of distal radius fractures显示文摘 | Nellans K W Kowalski E Chung K C | 2012 | Hand Clin2012，28，2： | 1 |
| 18 | Effects of physical and geochemical heterogeneities on mineral transformation and biomass accumulation during biostimulation experiments at Rifle, Colorado显示文摘 | LI L STEEFEL C I KOWALSKY M B | 2010 | Journal of Contaminant Hydrology2010，112，1234： | 1 |
| 19 | The relationship be-tween nurse practice environment,nurse work characteristics,bumout and job outcome and quality of nursing care:a crosssec-tional survey显示文摘 | Van Bogaert P Kowalski C Weeks SM | 2013 | Int J Nurs Stud2013，50，12： | 1 |
| 20 | Response surface designs within a split-plot structure显示文摘 | Vining G G Kowalski S M Montgomery D C | 2005 | Journal of Quality Technology2005，37，2： | 1 |
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