Department of Internal Medicine, University of California-Davis Comprehensive Cancer Center, Sacramento, California.
Sarah Cannon Research Institute/Tennessee Oncology, PLLC, North Nashville, Tennessee.
Cancer. 2018 May 1;124(9):2010-2017. doi: 10.1002/cncr.31293. Epub 2018 Feb 22.
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 Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
针对程序性死亡配体 1（PD-L1）/程序性细胞死亡蛋白 1（PD-1）检查点的抗体可能会引起与这类治疗药物作用机制相关的不良反应（AE），且这些不良反应与传统化疗观察到的不良反应不同。
接受avelumab（一种人源抗 PD-L1 IgG1 抗体）治疗的晚期实体瘤患者纳入了 1 期 JAVELIN 实体瘤（1650 例患者）和 2 期 JAVELIN Merkel 200（88 例患者）试验，剂量为 10 mg/kg，每 2 周 1 次。采用美国国立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（TRAEs）进行分级。在事后分析中，通过扩展的 AE 列表和医学审查确定免疫相关 AE（irAE），并根据预先指定的监管活动医学词典（MedDRA）术语确定输注相关反应（IRR）和输注后≤1 天发生且≤2 天缓解的症状。
在分析的 1738 例患者中，≥3 级 TRAEs 发生率为 177 例（10.2%）；最常见的是疲劳（17 例；1.0%）和 IRR（10 例；0.6%）。107 例患者（6.2%）因 TRAEs 而停药，4 例患者（0.2%）因 TRAEs 而死亡。39 例（2.2%）发生≥3 级 irAE，34 例（2.0%）因 irAE 而停药。439 例（25.3%）发生 IRR 或相关症状（0.5%[9 例]为 3 级，0.2%[3 例]为 4 级）。在发生 IRR 的 439 例患者中，79.5%在首次输注时发生 IRR，在发生 IRR 的 439 例患者中，98.6%在首次输注后的前 4 剂中发生 IRR，35 例（2.0%）因 IRR 而停药。
avelumab 总体耐受性良好，安全性可管理。少数患者发生≥3 级 TRAEs 或 irAE，停药并不常见。IRR 主要发生在首次输注时，反复发生的情况并不常见。癌症 2018；124:2010-7。© 2018 美国癌症协会。美国癌症协会出版的《癌症》杂志由 Wiley Periodicals, Inc. 以知识共享署名-非商业性使用-相同方式共享 4.0 国际许可协议获得授权。这是在知识共享许可下的文本，在符合该许可条款的情况下，允许在任何媒介中不受限制地使用、分发和复制该作品，前提是原始作品被正确引用并且不用于商业目的。
