Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Division of Hematology-Oncology, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Int J Infect Dis. 2021 May;106:142-154. doi: 10.1016/j.ijid.2021.03.063. Epub 2021 Mar 23.
Observational and experimental studies suggest that the use of antibiotics close to administration of immune checkpoint inhibitors (ICI) can have a negative effect on tumour response and patient survival, due to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells.
A systematic search of PUBMED and EMBASE was undertaken for studies published between 1 January 2017 and 1 June 2020, evaluating the association between the use of antibiotics and clinical outcomes in patients with cancer treated with ICIs. A meta-analysis of the association between the use of antibiotics and clinical outcomes was also performed.
Forty-eight studies met the inclusion criteria (12,794 patients). Use of antibiotics was associated with shorter overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.59-2.22; adjusted HR 1.87, 95% CI 1.55-2.25] and progression-free survival (HR 1.52, 95% CI 1.36-1.70; adjusted HR 1.93, 95% CI 1.59-2.36), decreased response rate [odds ratio (OR) 0.54, 95% CI 0.34-0.86] and more disease progression (OR 2.00, 95% CI 1.27-3.14). The negative association between the use of antibiotics and progression-free survival was stronger in patients with renal cell carcinoma or melanoma compared with lung cancer. Only antibiotic administration >1 month prior to ICI initiation was associated with increased disease progression. Heterogeneity was substantial for all outcomes.
Recent use of antibiotics in patients with cancer treated with ICIs was associated with worse clinical outcomes. Such patients may benefit from dedicated antimicrobial stewardship programmes.
观察性和实验研究表明，由于微生物组失调和宿主对肿瘤细胞免疫反应的抑制，抗生素在免疫检查点抑制剂 (ICI) 给药附近的使用会对肿瘤反应和患者生存产生负面影响。
对 2017 年 1 月 1 日至 2020 年 6 月 1 日期间发表的评估癌症患者使用抗生素与 ICI 治疗临床结局之间关联的研究进行了 PUBMED 和 EMBASE 的系统检索。还对抗生素使用与临床结局之间的关联进行了荟萃分析。
符合纳入标准的 48 项研究（12794 例患者）。使用抗生素与总生存期缩短相关[风险比 (HR) 1.88，95%置信区间 (CI) 1.59-2.22；调整 HR 1.87，95% CI 1.55-2.25]和无进展生存期 (HR 1.52，95% CI 1.36-1.70；调整 HR 1.93，95% CI 1.59-2.36)，降低了反应率[比值比 (OR) 0.54，95% CI 0.34-0.86]和更多的疾病进展 (OR 2.00，95% CI 1.27-3.14)。与肺癌相比，抗生素使用与肾细胞癌或黑色素瘤患者的无进展生存期之间的负相关更强。只有在 ICI 开始前>1 个月使用抗生素与疾病进展增加相关。所有结局的异质性都很大。
最近在接受 ICI 治疗的癌症患者中使用抗生素与更差的临床结局相关。此类患者可能受益于专门的抗菌药物管理计划。
