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环氧化酶抑制剂的使用对非小细胞肺癌免疫治疗疗效的影响。

Effect of cyclooxygenase inhibitor use on immunotherapy efficacy in non-small cell lung cancer.

机构信息

Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.

Department of Drug Discovery for Lung Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

出版信息

Thorac Cancer. 2021 Mar;12(6):949-957. doi: 10.1111/1759-7714.13845. Epub 2021 Feb 9.

Abstract

BACKGROUND

A synergistic effect of cyclooxygenase inhibitors (COX-I) and immune checkpoint inhibitors (ICIs) has been suggested. However, the impact of COX-I on the efficacy of ICIs is unclear. Here, we aimed to evaluate the relationship between COX-I use and the efficacy of ICI in patients with non-small cell lung cancer (NSCLC).

METHODS

We retrospectively reviewed NSCLC patients who received ICI monotherapy. We defined COX-I use as regular use of COX-I other than low-dose aspirin during the initiation of ICIs to the first evaluation of efficacy. The efficacy of ICIs was evaluated with response rate (RR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Differences in baseline characteristics by COX-I use were controlled by using an inverse probability of treatment weighting (IPW) adjusted analysis.

RESULTS

A total of 198 patients with NSCLC received ICIs; 128, 50, and 20 patients received nivolumab, pembrolizumab, and atezolizumab, respectively; there were 65 (32.8%) COX-I users. While there was no significant difference in RR (15.4% vs. 13.5%; p = 0.828), DCR (41.5% vs. 49.6%; p = 0.294), PFS (median, 2.69 vs. 3.68 months; 95% confidence intervals [CI], 1.77-5.19 vs. 2.20-4.60 months; p = 0.630), COX-I users had significantly shorter OS than non-COX-I users (median, 6.08 vs. 16.10 months; 95% CI: 3.78-11.66 vs. 9.49-19.68 months; p = 0.003). On IPW adjusted analysis, there was no significant difference in OS (median, 7.85 vs. 15.11 months; 95% CI: 5.03-14.92 vs. 9.49-19.32 months; p = 0.081).

CONCLUSIONS

There was no additional or negative impact of COX-I use on the efficacy of ICIs in NSCLC.

摘要

背景

已经提出环氧化酶抑制剂(COX-I)和免疫检查点抑制剂(ICIs)的协同作用。然而,COX-I 对 ICI 疗效的影响尚不清楚。在这里,我们旨在评估 COX-I 对非小细胞肺癌(NSCLC)患者接受 ICI 单药治疗的疗效的影响。

方法

我们回顾性地回顾了接受 ICI 单药治疗的 NSCLC 患者。我们将 COX-I 定义为在开始使用 ICI 至首次评估疗效期间,除低剂量阿司匹林外,常规使用 COX-I。ICI 的疗效通过反应率(RR)、疾病控制率(DCR)、无进展生存期(PFS)和总生存期(OS)进行评估。通过使用逆概率治疗加权(IPW)调整分析来控制 COX-I 使用者与非 COX-I 使用者之间的基线特征差异。

结果

共 198 例 NSCLC 患者接受 ICI 治疗;128、50 和 20 例患者分别接受纳武单抗、帕博丽珠单抗和阿特珠单抗治疗;65 例(32.8%)为 COX-I 使用者。RR(15.4%对 13.5%;p=0.828)、DCR(41.5%对 49.6%;p=0.294)和 PFS(中位数,2.69 对 3.68 个月;95%CI:1.77-5.19 对 2.20-4.60 个月;p=0.630)无显著差异,COX-I 使用者的 OS 明显短于非 COX-I 使用者(中位数,6.08 对 16.10 个月;95%CI:3.78-11.66 对 9.49-19.68 个月;p=0.003)。在 IPW 调整分析中,OS 无显著差异(中位数,7.85 对 15.11 个月;95%CI:5.03-14.92 对 9.49-19.32 个月;p=0.081)。

结论

COX-I 的使用对 NSCLC 患者的 ICI 疗效没有额外的或负面的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582a/7952791/32acd39adf5e/TCA-12-949-g002.jpg

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