Department of Oncology, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China.
Int Immunopharmacol. 2020 Nov;88:106876. doi: 10.1016/j.intimp.2020.106876. Epub 2020 Aug 12.
Immune checkpoint inhibitors (ICIs) have recently achieved inspiring performance in improving the prognosis of various solid tumors. Gut microbiome plays a crucial modulatory role in the efficacy of ICIs, which can be influenced by antibiotic (ATB) administration. In this meta-analysis, we aimed to clarify the correlations of ATB administration with the prognosis of solid cancer patients receiving ICI treatment.
The eligible literatures were searched using PubMed, Cochrane Library, Web of Science, and Clinical trials.gov databases before 29 February 2020. The correlations of ATB administration with overall survival (OS) and progression-free survival (PFS) were determined using Hazard ratios (HRs) coupled with 95% confidence intervals (CIs).
A total of 33 studies enrolling 5565 solid cancer patients receiving ICI treatment were included in this meta-analysis. As a whole, ATB administration was significantly correlated worse OS (HR = 1.76, 95%CI = 1.41-2.19, P < 0.00001) and PFS (HR = 1.76, 95%CI = 1.47-2.12, P < 0.00001). This significant association was then observed in the subgroup analysis based on region (except for OS in Europe), sample size, age, therapeutic strategy and ICI type. The similar results were also found in subgroup analysis for lung, renal cell (except for OS) and other cancers (such as melanoma) but not for mixed cancers. In addition, the ICI efficacy was more likely to be diminished by ATB administration within a time frame from 60 days before to 60 days after ICI initiation.
ATBs should be used cautiously in solid cancer patients receiving ICIs. However, further validations are still essential due to existing publication bias.
免疫检查点抑制剂（ICIs）最近在改善各种实体瘤的预后方面取得了令人鼓舞的效果。肠道微生物群在 ICI 的疗效中起着关键的调节作用，而抗生素（ATB）的使用会影响肠道微生物群。在这项荟萃分析中，我们旨在阐明 ATB 给药与接受 ICI 治疗的实体癌患者预后之间的相关性。
在 2020 年 2 月 29 日之前，使用 PubMed、Cochrane 图书馆、Web of Science 和 ClinicalTrials.gov 数据库搜索合格文献。使用风险比（HR）及其 95%置信区间（CI）确定 ATB 给药与总生存期（OS）和无进展生存期（PFS）的相关性。
这项荟萃分析共纳入了 33 项研究，共纳入了 5565 名接受 ICI 治疗的实体癌患者。总的来说，ATB 给药与较差的 OS（HR=1.76，95%CI=1.41-2.19，P<0.00001）和 PFS（HR=1.76，95%CI=1.47-2.12，P<0.00001）显著相关。基于地域（欧洲的 OS 除外）、样本量、年龄、治疗策略和 ICI 类型的亚组分析也观察到了这种显著的相关性。在肺、肾细胞癌（OS 除外）和其他癌症（如黑色素瘤）的亚组分析中也得到了类似的结果，但在混合癌症中则不然。此外，在 ICI 开始前 60 天至开始后 60 天内，ATB 给药更有可能降低 ICI 的疗效。
在接受 ICI 治疗的实体癌患者中，应谨慎使用 ATB。然而，由于存在发表偏倚，仍需要进一步的验证。
