Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis
Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis
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DOI：
10.1016/j.cllc.2018.09.005
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发表时间：
2019-01-01
影响因子：
3.6
通讯作者：
Lesperance, Mary
中科院分区：
文献类型：
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作者：
Ksienski, Doran;Wai, Elaine S.;Lesperance, Mary
Nivolumab和Pembrolizumab可导致免疫相关不良事件（irAE）。在这项对加拿大不列颠哥伦比亚省接受程序性死亡1抗体的晚期非小细胞肺癌患者的回顾性图表审查中，与连续治疗的患者相比，因irAE而中断治疗与中位总生存期（OS）较低相关。nivolumab治疗的患者中结肠炎的发生与未发生colis.Introduction的患者的OS较短相关：程序性死亡1抗体（PD-1 Ab）nivolumab和pembrolizumab改善晚期非小细胞肺癌（NSCLC）的总生存期（OS）。我们评估了免疫相关不良事件（irAE）和因irAE中断治疗与PD-1 Ab治疗晚期NSCLC临床疗效的相关性。患者和方法：确定了2015年6月至2017年11月在BC Cancer接受PD-1 Ab治疗的晚期NSCLC患者。从图表审查中提取irAE的人口统计学、肿瘤、治疗详情以及频率和级别（不良事件通用术语标准，第4.0版）。生成PD-1 Ab给药开始后OS的Kaplan-Meier曲线。采用考克斯比例风险回归模型进行多变量分析，包括6周和12周的标志分析。结果：在271例患者的队列中，在116例患者（42.8%）中观察到irAE。发生结肠炎的纳武利尤单抗接受者的OS低于在6周里程碑（P = .010）和12周里程碑（P = .072）时未发生结肠炎的接受者。对于整个队列，56例患者（20.7%）因irAE需要中断治疗。治疗中断与6周里程碑（P = 0.005）和12周里程碑（P = 0.008）的OS较低相关。6周里程碑多变量分析确定Charlson合并症指数评分为3或更高、东部肿瘤协作组体力状态为2或更高、存在肝转移和irAE大于2级与无irAE与OS降低相关（均P <0.05）。结论：与连续PD-1 Ab治疗相比，irAE导致的治疗中断与较低的中位OS相关。重度irAE患者的OS较短可能反映了在irAE治疗算法方面需要改善医生教育。(C)2018爱思唯尔公司All rights reserved.
Nivolumab and pembrolizumab can cause immune-related adverse events (irAE). In this retrospective chart review of advanced non-small-cell lung cancer patients receiving programmed death 1 antibodies in British Columbia, Canada, treatment interruption due to irAE was associated with a lower median overall survival (OS) than those treated continuously. Development of colitis in nivolumab-treated patients was associated with shorter OS than for patients who did not develop colitis.Introduction: The programmed death 1 antibodies (PD-1 Ab) nivolumab and pembrolizumab improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). We evaluated the correlation between immune-related adverse events (irAE) and treatment interruption due to irAE on clinical efficacy of PD-1 Ab in advanced NSCLC. Patients and Methods: Advanced NSCLC patients treated with PD-1 Ab between June 2015 to November 2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Common Terminology Criteria for Adverse Events, version 4.0) of irAE were abstracted from chart review. Kaplan-Meier curves of OS from initiation of PD-1 Ab were generated. Multivariable analysis with 6- and 12-week landmark analysis was performed by Cox proportional hazard regression models. Results: In a cohort of 271 patients, irAEs were observed in 116 patients (42.8%). Nivolumab recipients developing colitis had lower OS compared to those who did not at the 6-week landmark (P = .010) and 12-week landmark (P = .072). For the entire cohort, 56 patients (20.7%) needed treatment interruption because of an irAE. Treatment interruption correlated with lower OS at the 6-week landmark (P = .005) and 12-week landmark (P = .008). Six-week landmark multivariable analysis identified Charlson Comorbidity Index score of 3 or higher, Eastern Cooperative Oncology Group Performance Status of 2 or higher, presence of liver metastases, and irAE greater than grade 2 versus no irAE to be associated with decreased OS (each P < .05). Conclusion: Treatment interruption due to irAE was associated with a lower median OS compared to continuous PD-1 Ab therapy. Shorter OS seen with severe irAE might reflect the need for improved physician education in irAE treatment algorithms. (C) 2018 Elsevier Inc. All rights reserved.