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帕博利珠单抗联合化疗治疗鳞状非小细胞肺癌
Pembrolizumab plus Chemotherapy for Squamous Non–Small-Cell Lung Cancer


Luis Paz-Ares ... 肿瘤 呼吸系统疾病 • 2018.11.22
相关阅读
• 帕博利珠单抗与化疗治疗PD-L1阳性非小细胞肺癌的比较研究 • 帕博利珠单抗(pembrolizumab)可作为非小细胞肺癌的一线治疗吗 • 帕博利珠单抗治疗转移性非小细胞肺癌

摘要


背景

转移性鳞状非小细胞肺癌(NSCLC)的标准一线治疗是铂类化疗或帕博利珠单抗(用于有≥50%肿瘤细胞表达程序性死亡蛋白配体-1 [PD-L1]的患者)。最近,帕博利珠单抗联合化疗被证明可显著延长非鳞状NSCLC患者的总生存期。

 

方法

在这项双盲3期试验中,我们以1∶1的比例将559例未经治疗的转移性鳞状NSCLC患者随机分组,分别接受200 mg帕博利珠单抗或生理盐水安慰剂治疗,治疗持续长达35个周期;所有患者在前4个周期也接受卡铂联合紫杉醇或纳米颗粒白蛋白结合型[nab]–紫杉醇治疗。主要终点是总生存期和无进展生存期。

 

结果

经过中位7.8个月的随访,帕博利珠单抗联合治疗组的中位总生存期为15.9个月(95%置信区间[CI],13.2至未达到),安慰剂联合治疗组为11.3个月(95% CI,9.5~14.8)(死亡的风险比,0.64;95% CI,0.49~0.85;P<0.001)。不论PD-L1的表达水平如何,总生存获益一致。帕博利珠单抗联合治疗组的中位无进展生存期为6.4个月(95% CI,6.2~8.3),安慰剂联合治疗组为4.8个月(95% CI,4.3~5.7)(疾病进展或死亡的风险比,0.56;95% CI,0.45~0.70;P<0.001)。帕博利珠单抗联合治疗组69.8%的患者和安慰剂联合治疗组68.2%的患者发生了3级或更高级别的不良事件。帕博利珠单抗联合治疗组因不良事件而停止治疗的情况比安慰剂联合治疗组常见(13.3% vs. 6.4%)。

 

结论

在既往未经治疗的转移性鳞状NSCLC患者中,与仅接受卡铂加紫杉醇或纳米颗粒白蛋白结合型紫杉醇化疗相比,在化疗的基础上加用帕博利珠单抗使患者达到了显著较长的总生存期和无进展生存期(由默沙东公司资助;KEYNOTE-407在ClinicalTrials.gov 注册号为NCT02775435)。





作者信息

Luis Paz-Ares, M.D., Alexander Luft, M.D., David Vicente, M.D., Ali Tafreshi, M.D., Mahmut Gümüş, M.D., Julien Mazières, M.D., Ph.D., Barbara Hermes, M.D., Filiz Çay Şenler, M.D., Tibor Csőszi, M.D., Andrea Fülöp, M.D., Jerónimo Rodríguez-Cid, M.D., Jonathan Wilson, M.D., Shunichi Sugawara, M.D., Ph.D., Terufumi Kato, M.D., Ki Hyeong Lee, M.D., Ying Cheng, M.D., Ph.D., Silvia Novello, M.D., Ph.D., Balazs Halmos, M.D., Xiaodong Li, Ph.D., Gregory M. Lubiniecki, M.D., Bilal Piperdi, M.D., and Dariusz M. Kowalski, M.D. for the KEYNOTE-407 Investigators*
From Hospital Universitario 12 de Octubre, Spanish National Cancer Research Center, Universidad Complutense and Ciberonc, Madrid (L.P.-A.), and Hospital Universitario Virgen Macarena, Seville (D.V.) — both in Spain; Leningrad Regional Clinical Hospital, St. Petersburg, Russia (A.L.); Wollongong Oncology and Wollongong Private Hospital, Wollongong, NSW, Australia (A.T.); Istanbul Medeniyet University Hospital, Istanbul (M.G.), and Ankara University, Ankara (F.Ç.Ş.) — both in Turkey; Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France (J.M.); Universitätsklinikum Tübingen, Tübingen, Germany (B. Hermes); Jász-Nagykun-Szolnok County Hospital, Szolnok (T.C.), and Országos Korányi TBC és Pulmonológiai Intézet, Budapest (A.F.) — both in Hungary; Oncology Center, Medica Sur Hospital, Mexico City (J.R.-C.); Humber River Regional Hospital, Toronto (J.W.); Sendai Kousei Hospital, Sendai (S.S.), and the Kanagawa Cancer Center, Yokohama (T.K.) — both in Japan; Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju, South Korea (K.H.L.); Jilin Cancer Hospital, Changchun, China (Y.C.); University of Turin, Orbassano, Italy (S.N.); Montefiore Medical Center–Albert Einstein College of Medicine, New York (B. Halmos); Merck, Kenilworth, NJ (X.L., G.M.L., B.P.); and the Maria Skłodowska-Curie Institute of Oncology, Warsaw, Poland (D.M.K.). Address reprint requests to Dr. Paz-Ares at the Department of Medical Oncology, Hospital Universitario 12 de Octubre, Avenida de Córdoba, Madrid 28041, Spain, or at lpazaresr@seom.org. *A complete list of investigators who participated in the KEYNOTE-407 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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