Division of Pharmacy, National Cancer Center Hospital East, Chiba, Japan.
Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, Tokyo, Japan.
Thorac Cancer. 2021 Jul;12(13):1983-1994. doi: 10.1111/1759-7714.14001. Epub 2021 May 14.
It has recently been suggested that concomitant medication may affect the clinical outcome of patients treated with immune checkpoint inhibitors (ICIs). However, only a few studies on the impact of concomitant medication on immune-related adverse events (irAEs) have previously been reported. Here, we aimed to determine the impact of concomitant medication on the efficacy and safety of ICIs.
We retrospectively analyzed the data of 300 patients treated with nivolumab or pembrolizumab for advanced non-small cell lung cancer (NSCLC) between January 2016 and July 2018. Multivariate logistic regression analysis was used to assess the effect of concomitant medication on treatment response or irAEs. A multivariate Cox proportional hazards model was used to evaluate concomitant medication-related factors associated with time-to-treatment failure or overall survival (OS).
A total of 70 patients responded to treatment and 137 experienced irAEs. The response rate and incidence of irAEs in patients treated with ICIs were not significantly associated with concomitant medication. Multivariate analysis showed that the use of opioids was an independent factor (time-to-treatment failure: hazard ratio 1.39, p = 0.021, OS: hazard ratio 1.54, p = 0.007).
The efficacy and safety of nivolumab or pembrolizumab in the treatment of patients with advanced NSCLC were not significantly influenced by concomitant medication. However, opioid usage might be associated with shorter OS in patients treated with these ICIs. Further mechanistic investigations should explore whether these associations are purely prognostic or contribute to ICI resistance.
最近有人提出,伴随用药可能会影响接受免疫检查点抑制剂(ICI)治疗的患者的临床结局。然而,此前仅有少数研究报告了伴随用药对免疫相关不良事件(irAEs)的影响。在此,我们旨在确定伴随用药对 ICI 疗效和安全性的影响。
我们回顾性分析了 2016 年 1 月至 2018 年 7 月期间接受纳武利尤单抗或帕博利珠单抗治疗的 300 例晚期非小细胞肺癌(NSCLC)患者的数据。采用多变量逻辑回归分析评估伴随用药对治疗反应或 irAEs 的影响。采用多变量 Cox 比例风险模型评估与治疗失败时间或总生存期(OS)相关的伴随用药相关因素。
共有 70 例患者对治疗有反应,137 例患者发生 irAEs。ICI 治疗患者的反应率和 irAEs 发生率与伴随用药无显著相关性。多变量分析显示,使用阿片类药物是一个独立的因素(治疗失败时间:风险比 1.39,p=0.021,OS:风险比 1.54,p=0.007)。
纳武利尤单抗或帕博利珠单抗治疗晚期 NSCLC 患者的疗效和安全性不受伴随用药的显著影响。然而,阿片类药物的使用可能与这些 ICI 治疗患者的 OS 更短有关。进一步的机制研究应探讨这些关联是否纯粹是预后因素,还是导致 ICI 耐药的因素。