INTRODUCTION Immune checkpoint inhibitors (ICI) have dramatically improved patient outcomes in a variety of tumor types, but with variable efficacy. Recent research has suggested that antibiotic- induced disruption of the microbiota may impact ICI efficacy. METHODS We performed a systematic review and meta-analysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with non-small-cell lung carcinoma (NSCLC) treated with ICI. We systematically searched Medline, the Cochrane Library, and major oncology conferences proceedings. Eligible studies mentioned hazard ratio (HR) or Kaplan-Meier curves for progression-free survival (PFS) or overall survival (OS) according to antibiotics exposure before and/or during ICI treatment. RESULTS We identified 23 eligible studies. The impact of antibiotics was then evaluated in 2,208 patients for PFS and 5,560 for OS. For both PFS and OS meta-analyses, the between-study heterogeneity was high (Higgins and Thompson I2 of 69% and 80%, respectively). The pooled HR was 1.47 (95% CI [1.13;1.90]) for PFS and 1.69 (95% CI [1.25; 2.29]) for OS showing a significantly reduced survival in NSCLC patients exposed to antibiotics. The median OS was reduced on average by 6.7 months (95% CI [5.1; 8.4]) in patients exposed to antibiotics. The effect appears to depend on the time window of exposure with stronger effects reported when patients took antibiotics [-60 days; +60 days] around ICI initiation. CONCLUSION In NSCLC patients, the findings of the meta-analysis indicate that antibiotic use before or during treatment with ICI leads to a median OS decreased by more than 6 months. Specifically, exposure shortly before or after ICI initiation seems to be particularly detrimental, whereas antibiotic use later during disease course does not seem to alter survival. Since PFS and OS were difficult to compare between studies because of the heterogeneity and the multiple confounders factors identified, further studies are needed to strengthen the understanding of the phenomenon.

中文翻译：

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非小细胞肺癌免疫治疗疗效和抗生素使用：系统评价和荟萃分析

介绍 免疫检查点抑制剂 (ICI) 已显着改善了多种肿瘤类型的患者预后，但疗效各不相同。最近的研究表明，抗生素诱导的微生物群破坏可能会影响 ICI 的疗效。方法 我们对评估抗生素使用对经 ICI 治疗的非小细胞肺癌 (NSCLC) 患者生存影响的研究进行了系统回顾和荟萃分析。我们系统地检索了 Medline、Cochrane 图书馆和主要肿瘤学会议论文集。符合条件的研究根据 ICI 治疗前和/或治疗期间的抗生素暴露情况提到了无进展生存期 (PFS) 或总生存期 (OS) 的风险比 (HR) 或 Kaplan-Meier 曲线。结果 我们确定了 23 项符合条件的研究。然后在 2,208 名 PFS 患者和 5,560 名 OS 患者中评估了抗生素的影响。对于 PFS 和 OS 荟萃分析，研究之间的异质性很高（Higgins 和 Thompson I2 分别为 69% 和 80%）。PFS 的汇总 HR 为 1.47（95% CI [1.13;1.90]），OS 的汇总 HR 为 1.69（95% CI [1.25;2.29]），表明暴露于抗生素的 NSCLC 患者的生存率显着降低。暴露于抗生素的患者的中位 OS 平均降低了 6.7 个月（95% CI [5.1; 8.4]）。效果似乎取决于暴露的时间窗口，当患者服用抗生素时 [-60 天；+60 天] 在 ICI 启动前后。结论 在 NSCLC 患者中，荟萃分析的结果表明，在 ICI 治疗前或治疗期间使用抗生素导致中位 OS 降低超过 6 个月。具体而言，在 ICI 开始之前或之后不久暴露似乎特别有害，而在病程后期使用抗生素似乎不会改变生存。由于异质性和确定的多个混杂因素，研究之间难以比较 PFS 和 OS，因此需要进一步研究以加强对这一现象的理解。