Early Immune-Related Adverse Events and Association with Outcome in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab: A Prospective Cohort Study
Early Immune-Related Adverse Events and Association with Outcome in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab: A Prospective Cohort Study
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DOI：
10.1016/j.jtho.2017.08.022
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发表时间：
2017-12-01
影响因子：
20.4
通讯作者：
Tomii, Keisuke
中科院分区：
文献类型：
--
作者：
Teraoka, Shunsuke;Fujimoto, Daichi;Tomii, Keisuke
引言：回顾性研究显示免疫相关不良事件（irAE）与更好的预后相关。然而，没有前瞻性临床试验已经进行，并知之甚少，关于irAE和NSCLC患者的治疗后与immunotherapy.Methods的结果之间的关联：我们进行了一项前瞻性队列研究的晚期NSCLC患者谁是治疗与nivolumab之间2016年1月至12月。研究了临床结果与nivolumab治疗开始后2至6周的irAE之间的相关性。IrAE由至少三个独立的医疗professionals.Results评估：共43例患者入组，包括19例irAE开始纳武利尤单抗治疗后2周。常见的irAE包括皮疹、发热和腹泻。有和无irAE的患者之间程序性细胞死亡配体1阳性肿瘤细胞表达没有显着差异。发生irAE的患者的客观缓解率和疾病控制率高于未发生irAE的患者（分别为37% vs 17%和74% vs 29% [p = 0.17和p < 0.01]）。发生irAE的患者的中位无进展生存期显著长于未发生irAE的患者（6.4个月[95%置信区间：2.5-未达到] vs 1.5个月[95%置信区间：1.2-2.3] [p = 0.01]）。这些结果与nivolumab治疗开始后6周有和无irAE的患者的结果相当。结论：早期irAE与免疫治疗后的更好结局相关。我们通过使用早期irAE预测了对纳武单抗的反应。需要进一步的研究来阐明这些关联的机制。(C)2017年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: Retrospective studies have shown immune related adverse events (irAEs) to be associated with better prognosis. However, no prospective clinical trials have been conducted, and little is known regarding the association between irAEs and the outcome of patients with NSCLC after treatment with immunotherapy.Methods: We conducted a prospective cohort study of patients with advanced NSCLC who were treated with nivolumab between January and December 2016. The association between clinical outcome and irAEs 2 to 6 weeks after commencement of nivolumab treatment was investigated. IrAEs were assessed by at least three independent medical professionals.Results: A total of 43 patients were enrolled, including 19 patients with irAEs 2 weeks after commencement of nivolumab treatment. Common irAEs included rash, pyrexia, and diarrhea. Programmed cell death ligand 1-positive tumor cell expression was not significantly different between patients with and without irAEs. The objective response and disease control rates were higher in patients with irAEs than in those without irAEs (37% versus 17% and 74% versus 29% [p = 0.17 and p < 0.01], respectively]). Patients with irAEs were associated with a significantly longer median progression-free survival than those without (6.4 months [95% confidence interval: 2.5-not reached] versus 1.5 months [95% confidence interval: 1.2-2.3] [p = 0.01]). These findings were comparable to those for patients with and without irAEs 6 weeks after commencement of nivolumab treatment.Conclusions: Early irAEs are associated with a better outcome after treatment with immunotherapy. We predicted responses to nivolumab by using early irAEs. Further research is needed to elucidate the mechanisms of these associations. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.