BC Cancer-Victoria, Victoria, British Columbia, Canada.
BC Cancer-Victoria, Victoria, British Columbia, Canada.
Clin Lung Cancer. 2019 Jan;20(1):e97-e106. doi: 10.1016/j.cllc.2018.09.005. Epub 2018 Sep 22.
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.
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.
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).
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.
程序性死亡 1 抗体（PD-1Ab）纳武利尤单抗和帕博利珠单抗可改善晚期非小细胞肺癌（NSCLC）患者的总生存期（OS）。我们评估了免疫相关不良事件（irAE）与因 irAE 而中断治疗之间的相关性，以评估 PD-1Ab 在晚期 NSCLC 中的临床疗效。
回顾性分析了 2015 年 6 月至 2017 年 11 月在 BC 癌症中心接受 PD-1Ab 治疗的晚期 NSCLC 患者。从病历中提取患者的人口统计学、肿瘤、治疗细节以及 irAE 的频率和分级（不良事件通用术语标准，第 4.0 版）。使用 PD-1Ab 起始时的 Kaplan-Meier 曲线生成 OS 曲线。采用 Cox 比例风险回归模型进行 6 周和 12 周时间点的多变量分析。
在 271 例患者队列中，116 例（42.8%）患者出现 irAE。发生结肠炎的纳武利尤单抗组患者在 6 周时间点（P =.010）和 12 周时间点（P =.072）的 OS 较低。对于整个队列，56 例（20.7%）患者因 irAE 而需要中断治疗。治疗中断与 6 周时间点（P =.005）和 12 周时间点（P =.008）的 OS 降低相关。6 周时间点的多变量分析发现Charlson 合并症指数评分≥3、东部肿瘤协作组体力状态评分≥2、肝转移存在以及 irAE 分级≥2 与降低 OS 相关（均 P ＜.05）。
与持续 PD-1Ab 治疗相比，因 irAE 而中断治疗与较低的中位 OS 相关。严重 irAE 导致的较短 OS 可能反映了需要加强 irAE 治疗方案的医生教育。
