Da Volterra, Paris, France.
Da Volterra, Paris, France; Ecole Polytechnique, Palaiseau, France.
J Thorac Oncol. 2020 Jul;15(7):1147-1159. doi: 10.1016/j.jtho.2020.03.002. Epub 2020 Mar 12.
Immune checkpoint inhibitors (ICIs) 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. We performed a systematic review and meta-analysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with NSCLC and treated with ICI. We systematically searched Medline, the Cochrane Library, and major oncology conferences proceedings. Eligible studies mentioned hazard ratio or Kaplan-Meier curves for progression-free survival (PFS) or overall survival (OS) based on antibiotic exposure before or during ICI treatment. We identified 23 eligible studies. The impact of antibiotics was then evaluated in 2208 patients for PFS and 5560 for OS. For both PFS and OS meta-analyses, the between-study heterogeneity was high (Higgins and Thompson I of 69% and 80%, respectively). The pooled hazard ratio was 1.47 (95% confidence interval [CI]: 1.13-1.90) for PFS and 1.69 (95% CI: 1.25-2.29) for OS revealing a significantly reduced survival in patients with NSCLC exposed to antibiotics. The median OS was reduced on average by 6.7 months (95% CI: 5.1-8.4) in the patients exposed to antibiotics. The effect seems to depend on the time window of exposure with stronger effects reported when the patients took antibiotics [-60 days; +60 days] around ICI initiation. In patients with NSCLC, 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. Because PFS and OS were difficult to compare between studies owing to heterogeneity and the multiple confounding factors identified, further studies are needed to strengthen the understanding of this phenomenon.
免疫检查点抑制剂 (ICIs) 在多种肿瘤类型中显著改善了患者的预后，但疗效不一。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。我们对评估抗生素使用对接受 ICI 治疗的 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的会议记录。合格的研究根据 ICI 治疗前或治疗期间抗生素暴露情况，提到了无进展生存期 (PFS) 或总生存期 (OS) 的风险比或 Kaplan-Meier 曲线。我们确定了 23 项合格的研究。然后，在 2208 名接受 PFS 治疗的患者和 5560 名接受 OS 治疗的患者中评估了抗生素的影响。对于 PFS 和 OS 的荟萃分析，研究之间的异质性均很高（Higgins 和 Thompson I 分别为 69%和 80%）。荟萃分析的合并风险比为 1.47（95%置信区间 [CI]：1.13-1.90），用于 PFS，1.69（95%CI：1.25-2.29）用于 OS，表明接受抗生素治疗的 NSCLC 患者的生存率显著降低。接受抗生素治疗的患者的中位 OS 平均降低了 6.7 个月（95%CI：5.1-8.4）。该效果似乎取决于暴露的时间窗口，在患者接受抗生素治疗时，当时间窗口在 ICI 起始前 [-60 天；+60 天] 时，报告的效果更强。在 NSCLC 患者中，荟萃分析的结果表明，在接受 ICI 治疗前或治疗期间使用抗生素会导致中位 OS 降低 6 个月以上。具体而言，在 ICI 起始前后短期暴露似乎特别有害，而在疾病过程中较晚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，难以在研究之间比较 PFS 和 OS，因此需要进一步的研究来加强对这一现象的理解。
