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阿替利珠单抗用于根据PD-L1选择的NSCLC患者的一线治疗
Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC


Roy S. Herbst ... 肿瘤 • 2020.10.01
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• 阿特珠单抗联合化疗一线治疗广泛期小细胞肺癌 • 广泛期小细胞肺癌的一线治疗:一种新标准治疗

精确选择NSCLC患者,让免疫治疗更加有的放矢

 

何雅億,王灏,周彩存*

同济大学附属上海市肺科医院肿瘤科

*通讯作者

 

自PD-1/PD-L1轴在肿瘤免疫抑制中的作用被揭示后,多种抑制该轴的免疫检查点抑制剂逐渐被开发用于肺癌患者的免疫治疗。CheckMate 017/057研究探索了PD-1抑制剂纳武利尤单抗单药在晚期NSCLC二线治疗效果,显示出其能提供优于化疗的生存获益。KEYNOTE-010研究探索并证实了PD-1抑制剂帕博利珠单抗单药在晚期NSCLC二线治疗优于化疗的疗效。这些研究促进了免疫检查点抑制剂进入晚期NSCLC患者二线治疗方案。

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摘要


背景

用于表达PD-L1的转移性非小细胞肺癌(NSCLC)患者的一线治疗时,抗程序性死亡受体配体1(PD-L1)单克隆抗体阿替利珠单抗与铂类化疗相比的疗效和安全性尚未明确。

 

方法

我们在既往未接受过化疗,并且SP142免疫组化检测结果显示≥1%的肿瘤细胞或≥1%的肿瘤浸润免疫细胞表达PD-L1的转移性非鳞状或鳞状NSCLC患者中开展了一项随机、开放标签、3期试验。我们以1∶1的比例将患者随机分配接受阿替利珠单抗治疗或化疗。我们在意向治疗人群患者(肿瘤在EGFR突变或ALK易位方面属于野生型)中根据PD-L1表达状态分级检验了总生存期(主要终点)。在EGFRALK野生型肿瘤患者人群中,我们还在根据两种PD-L1检测法和根据血液内肿瘤突变负荷定义的亚组中前瞻性地评估了总生存期和无进展生存期。

 

结果

本试验纳入了共计572例患者。在PD-L1表达最高的EGFRALK野生型肿瘤患者亚组(205例患者)中,阿替利珠单抗组的中位总生存期比化疗组长7.1个月(20.2个月vs. 13.1个月;死亡的风险比,0.59;P=0.01)。在安全性可评估的所有患者中,阿替利珠单抗组90.2%的患者和化疗组94.7%的患者发生了不良事件;两组分别有30.1%和52.5%的患者发生了3级或4级不良事件。在血液内肿瘤突变负荷高的亚组中,接受阿替利珠单抗治疗的患者的总生存期和无进展生存期较长。

 

结论

不论组织学类型如何,在PD-L1表达高的NSCLC患者中,与铂类化疗相比,阿替利珠单抗均显著延长了总生存期(由罗氏制药/基因泰克资助,IMpower110在ClinicalTrials.gov注册号为NCT02409342)。





作者信息

Roy S. Herbst, M.D., Ph.D., Giuseppe Giaccone, M.D., Ph.D., Filippo de Marinis, M.D., Niels Reinmuth, M.D., Alain Vergnenegre, M.D., Carlos H. Barrios, M.D., Masahiro Morise, M.D., Enriqueta Felip, M.D., Zoran Andric, M.D., Sarayut Geater, M.D., Mustafa Özgüroğlu, M.D., Wei Zou, Ph.D., Alan Sandler, M.D., Ida Enquist, Ph.D., Kimberly Komatsubara, M.D., Yu Deng, Ph.D., Hiroshi Kuriki, M.Sc., Xiaohui Wen, M.D., Mark McCleland, Ph.D., Simonetta Mocci, M.D., Ph.D., Jacek Jassem, M.D., Ph.D., and David R. Spigel, M.D.
From the Yale School of Medicine, New Haven, CT (R.S.H.); Weill Cornell Medical Center, New York (G.G.); the European Institute of Oncology, IRCCS, Milan (F.M.); Asklepios Lung Clinic, Munich-Gauting, Germany (N.R.); University Hospital Limoges, Limoges, France (A.V.); Centro de Pesquisa Clínica, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil (C.H.B.); Nagoya University Graduate School of Medicine, Aichi, Japan (M. Morise); Vall d’Hebron University Hospital, Barcelona (E.F.); Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia (Z.A.); Prince of Songkla University–Hat Yai, Songkhla, Thailand (S.G.); Istanbul University–Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey (M.O.); Genentech, South San Francisco, CA (W.Z., A.S., I.E., K.K., Y.D., H.K., X.W., M. McCleland, S.M.); the Medical University of Gdańsk, Gdansk, Poland (J.J.); and the Sarah Cannon Research Institute at Tennessee Oncology, Nashville (D.R.S.). Address reprint requests to Dr. Herbst at Medical Oncology, Yale Cancer Center, Yale School of Medicine, 333 Cedar St., P.O. Box 208028, New Haven, CT 06520-8028, or at roy.herbst@yale.edu.

 

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