Background

Pre-clinical and clinical data had revealed the gut microbiome plays a critical role in immune checkpoint inhibitors (ICIs) efficacy. This study was designed to investigate whether antibiotics (ATBs) affect the prognosis of malignancies treated with ICIs.

Methods

Electronic databases were searched to identify relevant trials that evaluated the impact of ATBs on ICIs efficacy. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by HRs with corresponding 95%CIs. Subgroup analyses were performed based on cancer type, study design, ICIs agent, and time of ATBs administration.

Results

Totally, 12,492 individuals in the 44 cohorts were recruited. Pooled results showed that ATBs administration was significantly correlated with a worse objective remission rate (ORR) (OR = 0.61, 95%CI (0.42–0.90), P = 0.0128), PFS (HR = 1.18, 95%CI (1.11–1.25), P < 0.0001), and OS (HR = 1.20, 95%CI (1.15–1.25), P < 0.0001) in patients treated with ICIs. In subgroup analyses, patients treated with ICIs exposed to ATBs suffered an evidently worse ORR in arms of renal cell carcinoma (RCC) (OR = 0.30, 95%CI (0.14–0.67), P = 0.0034), multiple (OR = 0.44, 95%CI (0.27–0.73), P = 0.0016), and before ICIs initiation (OR = 0.47, 95%CI (0.32–0.71), P = 0.0003) without heterogeneity; experienced a worse PFS and OS in arms of non-small cell lung cancer, melanoma, RCC, urothelial carcinoma, multiple, prospective, retrospective, PD-(L)1 alone, PD-(L)1 plus CTLA-4, before ICIs initiation, before ICIs initiation and concurrent, and before or after ICIs within 1 month, while a better PFS and OS in concurrent with ICIs arm.

Conclusions

ATBs administration was negatively associated with ORR, PFS and OS in malignancies treated with ICIs, while the time of ATBs exposure might impact ICIs efficacy.

中文翻译：

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抗生素对恶性肿瘤免疫检查点抑制剂功效的影响：基于44个队列的研究

背景

临床前和临床数据表明，肠道微生物组在免疫检查点抑制剂（ICIs）的功效中起着至关重要的作用。本研究旨在调查抗生素（ATB）是否会影响使用ICI治疗的恶性肿瘤的预后。

方法

搜索电子数据库以鉴定相关试验，这些试验评估了ATB对ICI疗效的影响。主要终点是通过HR和相应的95％CI测得的总体生存期（OS）和无进展生存期（PFS）。根据癌症类型，研究设计，ICIs药物和ATB施用时间进行亚组分析。

结果

总共招募了44个队列中的12,492个人。汇总结果显示，ATBs给药与较差的客观缓解率（ORR）显着相关（OR = 0.61，95％CI（0.42-0.90），P  = 0.0128），PFS（HR = 1.18，95 ％CI（1.11-1.25） ），P  <0.0001）和OS（HR = 1.20，95％CI（1.15–1.25），P  <0.0001）。在亚组分析中，接受ATB暴露的ICI治疗的患者肾细胞癌（RCC）的ORR明显较差（OR = 0.30，95％CI（0.14-0.67），P =  0.0034），多次（OR = 0.44， 95％CI（0.27–0.73），P  = 0.0016），以及在ICI启动之前（OR = 0.47，95％CI（0.32-0.71），P = 0.0003）没有异质性；在ICI之前，非小细胞肺癌，黑色素瘤，RCC，尿路上皮癌，多发性，前瞻性，回顾性，仅PD-（L）1，PD-（L）1加CTLA-4的患者经历了较差的PFS和OS启动，ICI启动和并发之前以及1个月内在ICI之前或之后，而与ICI并发的PFS和OS更好。

结论

在用ICIs治疗的恶性肿瘤中，ATBs的给药与ORR，PFS和OS呈负相关，而ATBs暴露的时间可能会影响ICIs的疗效。