University of Basel, Basel, Switzerland.
Department of Medical Oncology, University Hospital, Basel, Switzerland.
Cancer Chemother Pharmacol. 2020 Jan;85(1):121-131. doi: 10.1007/s00280-019-03993-1. Epub 2019 Nov 19.
In this study, we test the hypothesis that the use of ATB reduces the efficacy of PD(L)1-targeting mAb.
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).
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).
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.
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。
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。
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)。
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。