Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.
Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.
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DOI：
10.18632/oncotarget.21586
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发表时间：
2017-10-31
期刊：
影响因子：
--
通讯作者：
Dey M
中科院分区：
文献类型：
--
作者：
Filley AC;Henriquez M;Dey M
胶质母细胞瘤（GBM）是成人中最常见的侵袭性原发性脑肿瘤。GBM患者的中位生存期不到两年，是现代最大的治疗挑战之一。即使使用最好的治疗方法，复发率也接近100%，复发时的治疗选择也非常有限。Nivolumab是一种抗程序性细胞死亡-1（PD-1）单克隆抗体，在治疗各种晚期癌症方面提供了显著的临床益处，并代表了原发性和复发性GBM的有希望的治疗方法。CheckMate 143（NCT 02017717）是第一个在GBM背景下进行的PD通路抑制的大型随机临床试验，包括比较nivolumab和抗VEGF抗体贝伐单抗治疗复发性疾病。然而，最近在WFNOS 2017摘要中宣布的初步结果表明，nivolumab未能延长复发性GBM患者的总生存期，并且该试验的这一分支过早关闭。在这篇综述中，我们讨论了在GBM中靶向PD通路的基本概念，解决了在中枢神经系统恶性肿瘤中使用免疫检查点抑制剂的影响，为nivolumab未能延长复发性疾病患者生存期的可能原因提供了理论基础，并分析了免疫检查点抑制剂在GBM治疗中的未来作用。
Glioblastoma (GBM) is the most common, and aggressive, primary brain tumor in adults. With a median patient survival of less than two years, GBM represents one of the biggest therapeutic challenges of the modern era. Even with the best available treatment, recurrence rates are nearly 100% and therapeutic options at the time of relapse are extremely limited. Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, has provided significant clinical benefits in the treatment of various advanced cancers and represented a promising therapy for primary and recurrent GBM. CheckMate 143 (NCT 02017717) was the first large randomized clinical trial of PD pathway inhibition in the setting of GBM, including a comparison of nivolumab and the anti-VEGF antibody, bevacizumab, in the treatment of recurrent disease. However, preliminary results, recently announced in a WFNOS 2017 abstract, demonstrated a failure of nivolumab to prolong overall survival of patients with recurrent GBM, and this arm of the trial was prematurely closed. In this review, we discuss the basic concepts underlying the rational to target PD pathway in GBM, address implications of using immune checkpoint inhibitors in central nervous system malignancies, provide a rationale for possible reasons contributing to the failure of nivolumab to prolong survival in patients with recurrent disease, and analyze the future role of immune checkpoint inhibitors in the treatment of GBM.
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DOI：
10.4137/cmo.s7232
发表时间：
2011
期刊：
Clinical Medicine Insights. Oncology
影响因子：
--
作者：
Chamberlain MC
通讯作者：
Chamberlain MC
影响因子：
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作者：
Banks WA
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影响因子：
8.4
作者：
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Tornillo, Luigi
影响因子：
7.3
作者：
Derer A;Spiljar M;Bäumler M;Hecht M;Fietkau R;Frey B;Gaipl US
通讯作者：
Gaipl US
DOI：
10.1158/1078-0432.ccr-15-2839
发表时间：
2016-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Choueiri TK;Fishman MN;Escudier B;McDermott DF;Drake CG;Kluger H;Stadler WM;Perez-Gracia JL;McNeel DG;Curti B;Harrison MR;Plimack ER;Appleman L;Fong L;Albiges L;Cohen L;Young TC;Chasalow SD;Ross-Macdonald P;Srivastava S;Jure-Kunkel M;Kurland JF;Simon JS;Sznol M
通讯作者：
Sznol M