Non-small-cell lung cancer immunotherapy efficacy and antibiotic use: a systematic review and meta-analysis.

Abstract Introduction Immune checkpoint inhibitors (ICI) have dramatically improved patient outcomes in a variety of tumor types, but with variable efficacy. Recent research has suggested that antibiotic- induced disruption of the microbiota may impact ICI efficacy. Methods We performed a systematic review and meta-analysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with non-small-cell lung carcinoma (NSCLC) treated with ICI. We systematically searched Medline, the Cochrane Library, and major oncology conferences proceedings. Eligible studies mentioned hazard ratio (HR) or Kaplan–Meier curves for progression-free survival (PFS) or overall survival (OS) according to antibiotics exposure before and/or during ICI treatment. Results We identified 23 eligible studies. The impact of antibiotics was then evaluated in 2,208 patients for PFS and 5,560 for OS. For both PFS and OS meta-analyses, the between-study heterogeneity was high (Higgins and Thompson I2 of 69% and 80%, respectively). The pooled HR was 1.47 (95% CI [1.13;1.90]) for PFS and 1.69 (95% CI [1.25; 2.29]) for OS showing a significantly reduced survival in NSCLC patients exposed to antibiotics. The median OS was reduced on average by 6.7 months (95% CI [5.1; 8.4]) in patients exposed to antibiotics. The effect appears to depend on the time window of exposure with stronger effects reported when patients took antibiotics [−60 days; +60 days] around ICI initiation. Conclusion In NSCLC patients, 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. Specifically, 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. Since PFS and OS were difficult to compare between studies because of the heterogeneity and the multiple confounders factors identified, further studies are needed to strengthen the understanding of the phenomenon.