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

Int J Infect Dis. 2021 Mar 23:S1201-9712(21)00281-2. doi: 10.1016/j.ijid.2021.03.063. Online ahead of print.

ABSTRACT

OBJECTIVES: Observational and experimental studies suggest that antibiotic use close to administration of immune checkpoint inhibitors (ICI) can negatively affect tumor response and patient survival, due to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells.

METHODS: We conducted a systematic search of PUBMED and EMBASE for studies published between 1/1/17 and 6/1/20, evaluating the association between antibiotic use and clinical outcomes in cancer patients treated with ICI, and a meta-analysis of the association between antibiotics and clinical outcomes.

RESULTS: 48 studies fulfilled inclusion criteria (12,794 patients). Antibiotic use was associated with shorter overall (HR 1.88; 95% C.I. 1.59-2.22; adjusted HR 1.87; 95%C.I. 1.55-2.25), and progression-free survival (HR 1.52; 95%C.I. 1.36-1.70; adjusted HR1.93; 95%C.I. 1.59-2.36), decreased response rate (OR 0.54; 95%C.I. 0.34-0.86) and more disease progression (OR 2.00; 95%C.I. 1.27-3.14). The negative association with progression-free survival was stronger in renal cell carcinoma or melanoma than lung cancer. Only antibiotic administration>1 month prior to ICI initiation was associated with increased disease progression. Heterogeneity was substantial for all outcomes.

CONCLUSIONS: Recent antibiotic use in patients with cancer treated with ICI was associated with worse clinical outcomes. Such patients may benefit from dedicated antimicrobial stewardship programs.

PMID:33771672 | DOI:10.1016/j.ijid.2021.03.063