在一项涉及晚期非小细胞肺癌（NSCLC）患者的早期研究中，Nivolumab联合依普利单抗治疗的应答率优于Nivolumab单药治疗，尤其是表达程序性死亡配体-1（PD-L1）的肿瘤患者。但仍需进一步研究来评估Nivolumab联合依普利单抗治疗NSCLC的长期疗效。
在这项开放标签的临床3期试验中，研究人员招募了IV期或复发性NSCLC患者，将PD-L1表达水平为1%或以上的参与者按1：1：1随机分组，分别接受Nivolumab+依普利单抗、单独Nivolumab或化疗。将PD-L1表达水平低于1%的患者按1：1：1随机分为Nivolumab+依普利单抗、Nivolumab+化疗或单纯化疗。所有病人入组前均未接受过化疗。
在PD-L1表达水平为1%或以上的患者中，Nivolumab+依普利单抗组的中位总生存期为17.1个月，化疗组为14.9个月，2年总生存率分别为40.0%和32.8%。Nivolumab+依普利单抗组的中位缓解期为23.2个月，化疗组为6.2个月。在PD-L1表达水平低于1%的患者中，Nivolumab+依普利单抗组的中位总生存期为17.2个月，化疗组为12.2个月。在试验的所有患者中，Nivolumab+依普利单抗组的中位总生存期为17.1个月，化疗组为13.9个月。Nivolumab+依普利单抗组中有32.8%的患者发生3-4级治疗相关不良事件，化疗组为36.0%。
总之，Nivolumab+依普利单抗治疗NSCLC患者与单纯化疗相比，可显著延长总生存期，且与PD-L1表达水平无关。进一步随访亦表明未出现新的安全问题。
METHODS
In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. All the patients had received no previous chemotherapy. The primary end point reported here was overall survival with nivolumab plus ipilimumab as compared with chemotherapy in patients with a PD-L1 expression level of 1% or more.
RESULTS
Among the patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P=0.007), with 2-year overall survival rates of 40.0% and 32.8%, respectively. The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. The overall survival benefit was also observed in patients with a PD-L1 expression level of less than 1%, with a median duration of 17.2 months (95% CI, 12.8 to 22.0) with nivolumab plus ipilimumab and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy. Among all the patients in the trial, the median duration of overall survival was 17.1 months (95% CI, 15.2 to 19.9) with nivolumab plus ipilimumab and 13.9 months (95% CI, 12.2 to 15.1) with chemotherapy. The percentage of patients with grade 3 or 4 treatment-related adverse events in the overall population was 32.8% with nivolumab plus ipilimumab and 36.0% with chemotherapy.
CONCLUSIONS
First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up.
Nivolumab联合依普利单抗治疗晚期非小细胞肺癌
作者：小柯机器人 发布时间：2019/9/29 16:12:20
美国纪念斯隆·凯瑟琳癌症研究中心Matthew D. Hellmann等研究人员，分析了Nivolumab联合依普利单抗治疗晚期非小细胞肺癌的疗效。相关成果于2019年9月28日在线发表在《新英格兰医学杂志》上。
在一项涉及晚期非小细胞肺癌（NSCLC）患者的早期研究中，Nivolumab联合依普利单抗治疗的应答率优于Nivolumab单药治疗，尤其是表达程序性死亡配体-1（PD-L1）的肿瘤患者。但仍需进一步研究来评估Nivolumab联合依普利单抗治疗NSCLC的长期疗效。
在这项开放标签的临床3期试验中，研究人员招募了IV期或复发性NSCLC患者，将PD-L1表达水平为1%或以上的参与者按1：1：1随机分组，分别接受Nivolumab+依普利单抗、单独Nivolumab或化疗。将PD-L1表达水平低于1%的患者按1：1：1随机分为Nivolumab+依普利单抗、Nivolumab+化疗或单纯化疗。所有病人入组前均未接受过化疗。
在PD-L1表达水平为1%或以上的患者中，Nivolumab+依普利单抗组的中位总生存期为17.1个月，化疗组为14.9个月，2年总生存率分别为40.0%和32.8%。Nivolumab+依普利单抗组的中位缓解期为23.2个月，化疗组为6.2个月。在PD-L1表达水平低于1%的患者中，Nivolumab+依普利单抗组的中位总生存期为17.2个月，化疗组为12.2个月。在试验的所有患者中，Nivolumab+依普利单抗组的中位总生存期为17.1个月，化疗组为13.9个月。Nivolumab+依普利单抗组中有32.8%的患者发生3-4级治疗相关不良事件，化疗组为36.0%。
总之，Nivolumab+依普利单抗治疗NSCLC患者与单纯化疗相比，可显著延长总生存期，且与PD-L1表达水平无关。进一步随访亦表明未出现新的安全问题。
附：英文原文
Title:Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer
Author: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.
Issue&Volume:2019-09-28
Abstract:
BACKGROUND
In an early-phase study involving patients with advanced non–small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC.
In an early-phase study involving patients with advanced non–small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC.
METHODS
In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. All the patients had received no previous chemotherapy. The primary end point reported here was overall survival with nivolumab plus ipilimumab as compared with chemotherapy in patients with a PD-L1 expression level of 1% or more.
RESULTS
Among the patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P=0.007), with 2-year overall survival rates of 40.0% and 32.8%, respectively. The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. The overall survival benefit was also observed in patients with a PD-L1 expression level of less than 1%, with a median duration of 17.2 months (95% CI, 12.8 to 22.0) with nivolumab plus ipilimumab and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy. Among all the patients in the trial, the median duration of overall survival was 17.1 months (95% CI, 15.2 to 19.9) with nivolumab plus ipilimumab and 13.9 months (95% CI, 12.2 to 15.1) with chemotherapy. The percentage of patients with grade 3 or 4 treatment-related adverse events in the overall population was 32.8% with nivolumab plus ipilimumab and 36.0% with chemotherapy.
CONCLUSIONS
First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up.
DOI:10.1056/NEJMoa1910231
期刊信息
The New England Journal of Medicine：《新英格兰医学杂志》，创刊于1812年。隶属于麻省医学协会，最新IF：70.67
官方网址：http://www.nejm.org/
投稿链接：http://www.nejm.org/page/author-center/home