Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Abstract

ObjectivesObservational 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. MethodsA 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. ResultsForty-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. ConclusionsRecent 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.