Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials.
Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials.
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DOI：
10.1002/cncr.31293
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发表时间：
2018-05-01
期刊：
影响因子：
6.2
通讯作者：
Gulley JL
中科院分区：
文献类型：
--
作者：
Kelly K;Infante JR;Taylor MH;Patel MR;Wong DJ;Iannotti N;Mehnert JM;Loos AH;Koch H;Speit I;Gulley JL
靶向程序性死亡配体1（PD-L1）/程序性细胞死亡蛋白1（PD-1）检查点的抗体可能导致与该治疗类别的作用机制相关的不良事件（AE），并且与常规化疗观察到的不良事件不同。入组I期JAVELIN实体瘤（1650例患者）和II期JAVELIN默克尔200（88例患者）试验的晚期实体瘤患者接受avelumab（一种人抗PD-L1 IgG 1抗体）治疗，剂量为10 mg/kg，每2周一次。使用美国国家癌症研究所不良事件通用术语标准（第4.0版）对治疗相关AE（TRAE）进行分级。在事后分析中，通过扩展AE列表和医学审查确定免疫相关AE（irAE），并根据预先规定的国际医学用语词典（MedDRA）术语确定输注后≤2天发生的输注相关反应（IRR）和输注后≤1天发生的症状以及发作后≤2天消退的症状。在分析的1738例患者中，177例（10.2%）发生≥3级TRAE;最常见的是疲乏（17例患者; 1.0%）和IRR（10例患者; 0.6%）。TRAE导致107例患者（6.2%）停药，4例患者（0.2%）死亡。39例患者（2.2%）发生≥3级irAE，34例患者（2.0%）导致停药。439例患者发生IRR或相关症状（25.3%; 0.5% [9例患者]为3级，0.2% [3例患者]为4级）。在439例发生IRR的患者中，79.5%的患者在首次输注时发生IRR，98.6%的患者在前4次给药内发生IRR，35例患者（2.0%）导致停药。Avelumab通常被发现耐受性良好，并且具有可管理的安全性特征。少数患者发生≥3级TRAE或irAE，停药不常见。IRR主要发生在首次输注时，重复事件不常见。癌症2018;124：2010 - 7。版权所有© 2018作者.出版社：Wiley Periodicals，Inc.代表美国癌症协会这是一篇根据http://creativecommons.org/licenses/by-nc/4.0/许可证条款的开放获取文章，该许可证允许在任何媒体上使用，分发和复制，前提是原始作品被正确引用并且不用于商业目的。在目前对1期JAVELIN实体瘤和2期JAVELIN默克尔200试验中接受avelumab治疗的1738例患者进行的汇总分析中，≥3级治疗相关不良事件或任何级别免疫相关不良事件的发生率均较低。Avelumab通常耐受性良好，并且具有与其他抗程序性死亡配体1/程序性细胞死亡蛋白1抗体一致的可管理的安全性特征。
Antibodies targeting the programmed death‐ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti–PD‐L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment‐related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune‐related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion‐related reactions (IRRs) occurring ≤2 days after infusion and symptoms occurring ≤1 day after infusion and resolving ≤2 days after onset were identified based on prespecified Medical Dictionary for Regulatory Activities (MedDRA) terms. Of the 1738 patients analyzed, grade ≥3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade ≥3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%). Avelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010‐7. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. In the current pooled analysis of 1738 patients treated with avelumab in the phase 1 JAVELIN Solid Tumor and phase 2 JAVELIN Merkel 200 trials, the incidences of grade ≥3 treatment‐related adverse events or any‐grade immune‐related adverse events is reported to be low. Avelumab generally is well tolerated and has a manageable safety profile consistent with other anti–programmed death‐ligand 1/programmed cell death protein 1 antibodies.
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影响因子：
45.3
作者：
Massard, Christophe;Gordon, Michael S.;Segal, Neil H.
通讯作者：
Segal, Neil H.
DOI：
10.1016/s1470-2045(16)30364-3
发表时间：
2016-10
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Kaufman HL;Russell J;Hamid O;Bhatia S;Terheyden P;D'Angelo SP;Shih KC;Lebbé C;Linette GP;Milella M;Brownell I;Lewis KD;Lorch JH;Chin K;Mahnke L;von Heydebreck A;Cuillerot JM;Nghiem P
通讯作者：
Nghiem P
影响因子：
10.1
作者：
Stewart, Ross;Morrow, Michelle;McCourt, Matthew
通讯作者：
McCourt, Matthew
影响因子：
11.5
作者：
Patnaik, Amita;Kang, S. Peter;Tolcher, Anthony W.
通讯作者：
Tolcher, Anthony W.
影响因子：
10.9
作者：
Kaufman, Howard L.;Russell, Jeffery S.;Nghiem, Paul
通讯作者：
Nghiem, Paul