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纳武利尤单抗联合伊匹单抗治疗晚期非小细胞肺癌
Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer


Matthew D. Hellmann ... 肿瘤 呼吸系统疾病 • 2019.11.21
相关阅读
• 纳武利尤单抗联合伊匹单抗治疗NSCLC:最新生存期结果 • 纳武利尤单抗联合伊匹单抗一线治疗晚期非小细胞肺癌 • 纳武利尤单抗一线治疗Ⅳ期或复发性非小细胞肺癌

ESMO高光时刻后的深度思考:晚期肺癌一线双免疫治疗

 

梁乃新*,贾梓淇

北京协和医院胸外科

*通讯作者

 

自2014年底免疫检查点抑制剂获批应用于非小细胞肺癌(NSCLC)以来,免疫治疗为晚期NSCLC患者带来巨大的生存改善。目前已经有多个免疫检查点抑制剂治疗方案获批应用于晚期NSCLC的一线治疗,其中首先是基于PD-L1表达量而选择人群的单药治疗1,2

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摘要


背景

在一项对晚期非小细胞肺癌(NSCLC)患者开展的早期研究中,纳武利尤单抗+伊匹单抗联合治疗的缓解率高于纳武利尤单抗单药治疗,尤其是在肿瘤表达程序性死亡受体配体1(PD-L1)的患者中。我们需要数据来评估NSCLC患者接受纳武利尤单抗+伊匹单抗治疗的长期获益。

 

方法

在这项开放标签的3期试验中,我们以1∶1∶1的比例将PD-L1表达水平≥1%的Ⅳ期或复发性NSCLC患者随机分组,分别接受纳武利尤单抗+伊匹单抗治疗、纳武利尤单抗单药治疗或化疗,并且以1∶1∶1的比例将PD-L1表达水平<1%的患者随机分组,分别接受纳武利尤单抗+伊匹单抗治疗、纳武利尤单抗+化疗或者单独化疗。所有患者之前均未接受过化疗。本文报告的主要终点是在PD-L1表达水平≥1%的患者中,与化疗组相比,纳武利尤单抗+伊匹单抗治疗组的总生存期。

 

结果

在PD-L1表达水平≥1%的患者中,纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.1个月(95% CI,15.0~20.1)和14.9个月(95% CI,12.7~16.7)(P=0.007),2年总生存率分别为40.0%和32.8%。纳武利尤单抗+伊匹单抗组和化疗组的中位缓解持续时间分别为23.2个月和6.2个月。我们在PD-L1表达水平<1%的患者中也观察到了总生存期获益,纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.2个月(95% CI,12.8~22.0)和12.2个月(95% CI,9.2~14.3)。在本试验的全部患者中,纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.1个月(95% CI,15.2~19.9)和13.9个月(95% CI,12.2~15.1)。在总体人群中,纳武利尤单抗+伊匹单抗组和化疗组中发生3级或4级治疗相关性不良事件的患者百分比分别为32.8%和36.0%。

 

结论

在NSCLC患者中,纳武利尤单抗+伊匹单抗一线治疗组的总生存期超过化疗组,且与PD-L1表达水平无关。长期随访中未发现新的安全性问题(由百时美施贵宝和日本小野制药株式会社[Ono Pharmaceutical]资助;在ClinicalTrials.gov注册号为NCT02477826)。





作者信息

Matthew D. Hellmann, M.D., Luis Paz-Ares, M.D., Ph.D., Reyes Bernabe Caro, M.D., Ph.D., Bogdan Zurawski, M.D., Ph.D., Sang-We Kim, M.D., Ph.D., Enric Carcereny Costa, M.D., Keunchil Park, M.D., Ph.D., Aurelia Alexandru, M.D., Lorena Lupinacci, M.D., Emmanuel de la Mora Jimenez, M.D., Hiroshi Sakai, M.D., Istvan Albert, M.D., Alain Vergnenegre, M.D., Solange Peters, M.D., Ph.D., Konstantinos Syrigos, M.D., Ph.D., Fabrice Barlesi, M.D., Ph.D., Martin Reck, M.D., Ph.D., Hossein Borghaei, D.O., Julie R. Brahmer, M.D., Kenneth J. O’Byrne, M.D., William J. Geese, Ph.D., Prabhu Bhagavatheeswaran, Ph.D., Sridhar K. Rabindran, Ph.D., Ravi S. Kasinathan, Ph.D., Faith E. Nathan, M.D., and Suresh S. Ramalingam, M.D.
From the Memorial Sloan Kettering Cancer Center, New York (M.D.H.); Hospital Universitario Doce de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and Centro de Investigación Biomédica en Red de Cáncer, Madrid (L.P.-A.), Hospital Universitario Virgen Del Rocio, Seville (R.B.C.), and the Catalan Institute of Oncology–Germans Trias i Pujol Hospital, Badalona (E.C.C.) — all in Spain; Ambulatorium Chemioterapii, Bydgoszcz, Poland (B.Z.); the Asan Medical Center (S.-W.K.) and the Samsung Medical Center at Sungkyunkwan University School of Medicine (K.P.) — both in Seoul, South Korea; the Institute of Oncology Prof. Dr. Alexandru Trestioreanu, Bucharest, Romania (A.A.); the Hospital Italiano de Buenos Aires, Buenos Aires (L.L.); Instituto Jalisciense de Cancerologia, Guadalajara, Mexico (E.M.J.); the Saitama Cancer Center, Saitama, Japan (H.S.); Matrai Gyogyintezet, Matrahaza, Hungary (I.A.); Limoges University Hospital, Limoges (A.V.), and Aix-Marseille University, National Center for Scientific Research, INSERM, Centre de Recherche en Cancérologie de Marseille, Assistance Publique–Hôpitaux de Marseille, Marseille (F.B.) — all in France; Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland (S.P.); Sotiria General Hospital, National and Kapodistrian University of Athens, Athens (K.S.); Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany (M.R.); Fox Chase Cancer Center, Philadelphia (H.B.); Johns Hopkins Kimmel Cancer Center, Baltimore (J.R.B.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., P.B., S.K.R., R.S.K., F.E.N.); and Winship Cancer Institute, Emory University, Atlanta (S.S.R.). Address reprint requests to Dr. Hellmann at the Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, 885 2nd Ave., New York, NY 10017, or at hellmanm@mskcc.org. A complete list of the investigators in part 1 of the CheckMate 227 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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