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晚期非小细胞肺癌患者接受免疫检查点抑制剂治疗时抗生素的预测影响:抗生素免疫检查点抑制剂在晚期 NSCLC 中的应用。

Predictive impact of antibiotics in patients with advanced non small-cell lung cancer receiving immune checkpoint inhibitors : Antibiotics immune checkpoint inhibitors in advanced NSCLC.

机构信息

University of Basel, Basel, Switzerland.

Department of Medical Oncology, University Hospital, Basel, Switzerland.

出版信息

Cancer Chemother Pharmacol. 2020 Jan;85(1):121-131. doi: 10.1007/s00280-019-03993-1. Epub 2019 Nov 19.

Abstract

PURPOSE

In this study, we test the hypothesis that the use of ATB reduces the efficacy of PD(L)1-targeting mAb.

METHODS

We included patients with locally advanced, inoperable or metastatic, EGFR wildtype and ALK-negative non-small-cell lung cancer (NSCLC) who received a PD(L)1 targeting mAb (immune checkpoint inhibitor, ICI) between January 2013 and December 2017. The primary study objective was to assess the predictive impact of ATB use within 2 months prior to starting ICI treatment on overall survival from the time of starting ICI treatment (OS-ICI).

RESULTS

33 out of 218 evaluable patients (15.1%) received ATB within 2 months prior to starting ICI treatment. The use of ATB prior to starting ICI was associated with a lower rate of radiological response (18.2 vs. 28.3%, respectively, P = 0.02). PFS was significantly shorter in patients receiving ATB within 2 months prior to ICI compared to those not receiving ATB (median PFS 1.4 vs. 5.5 months, HR = 2.22, P < 0.01). OS-ICI was significantly shorter in NSCLC patients receiving ATB within 2 months prior to ICI compared to those not receiving ATB (median OS-ICI 1.8 vs. 15.4 months, HR = 2.61, P < 0.01; adjusted HR = 3.73, P < 0.01).

CONCLUSION

The results of this study suggest that ATB may have a deleterious effect in patients with advanced NSCLC receiving ICI treatment, and more research seems to be justified to explore potential mechanisms.

摘要

目的

本研究旨在检验以下假设,即抗生素(ATB)的使用会降低 PD(L)1 靶向单克隆抗体(mAb)的疗效。

方法

我们纳入了 2013 年 1 月至 2017 年 12 月期间接受 PD(L)1 靶向 mAb(免疫检查点抑制剂,ICI)治疗的局部晚期、不可手术或转移性、表皮生长因子受体(EGFR)野生型和间变性淋巴瘤激酶(ALK)阴性非小细胞肺癌(NSCLC)患者。主要研究目的是评估在开始 ICI 治疗前 2 个月内使用 ATB 对从开始 ICI 治疗起的总生存(ICI-OS)的预测影响。

结果

在 218 例可评估患者中,有 33 例(15.1%)在开始 ICI 治疗前 2 个月内接受了 ATB。在开始 ICI 治疗前使用 ATB 与较低的影像学缓解率相关(分别为 18.2%和 28.3%,P=0.02)。与未接受 ATB 的患者相比,在 ICI 治疗前 2 个月内接受 ATB 的患者的无进展生存期(PFS)明显缩短(中位 PFS 1.4 与 5.5 个月,HR=2.22,P<0.01)。与未接受 ATB 的患者相比,在 ICI 治疗前 2 个月内接受 ATB 的 NSCLC 患者的 ICI-OS 明显缩短(中位 ICI-OS 1.8 与 15.4 个月,HR=2.61,P<0.01;调整 HR=3.73,P<0.01)。

结论

本研究结果表明,ATB 可能对接受 ICI 治疗的晚期 NSCLC 患者产生有害影响,似乎有理由进行更多研究以探索潜在机制。

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