NSCLC Immunotherapy Efficacy and Antibiotic Use: A Systematic Review and Meta-Analysis

Immune checkpoint inhibitors (ICIs) have dramatically improved patient outcomes in a variety of tumor types, but with variable ef ficacy. Recent research has suggested that antibiotic-induced disruption of the microbiota may impact ICI ef ficacy. We performed a systematic review and meta-analysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with NSCLC and treated with ICI. We systematically searched Medline, the Cochrane Library, and major oncology conferences pro-ceedings. Eligible studies mentioned hazard ratio or Kaplan-Meier curves for progression-free survival (PFS) or overall survival (OS) based on antibiotic exposure before or during ICI treatment. We identi fied 23 eligible studies. The impact of antibiotics was then evaluated in 2208 patients for PFS and 5560 for OS. For both PFS and OS meta-analyses, the between-study heterogeneity was high (Hig-gins and Thompson I 2 of 69% and 80%, respectively). The pooled hazard ratio was 1.47 (95% con fidence interval [CI]: 1.13-1.90) for PFS and 1.69 (95% CI: 1.25-2.29) for OS revealing a signi ficantly reduced survival in patients with NSCLC exposed to antibiotics. The median OS was reduced on average by 6.7 months (95% CI: 5.1-8.4) in the patients exposed to antibiotics. The effect seems to depend on the time window of exposure with stronger effects reported when the patients took antibiotics [-60 days; +60 days] around ICI initiation. In patients with NSCLC, the findings of the meta-analysis indicate that antibiotic use before or during treatment with ICI leads to a median OS decreased by more than 6 months. Speci fically, exposure shortly before or after ICI initiation seems to be particularly detrimental, whereas antibiotic use later during disease course does not seem to alter survival. Because PFS and OS were dif ficult to compare between studies owing to het-erogeneity and the multiple confounding factors identi fied, further studies are needed to strengthen the understanding of this phenomenon. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.