Impact of concomitant antibiotic exposure on overall survival in patients with esophagogastric cancer treated with immune checkpoint inhibitors: A real-world cohort study.

11160 Background: Gut microbiota composition plays a critical role in mediating response to immune checkpoint inhibitors (ICIs). Antibiotic exposure has been associated with impaired ICI efficacy across tumor types; however, data specific to esophagogastric cancers remain limited. We evaluated the association between peritreatment antibiotic exposure and overall survival (OS) among patients with advanced esophagogastric cancer receiving ICIs in routine clinical practice. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with advanced or metastatic esophageal or gastric adenocarcinoma who received nivolumab- or pembrolizumab-based therapy between 2016 and 2024 were identified. Patients were categorized as antibiotic-exposed (receipt of systemic antibiotics within 60 days before or after ICI initiation) and non-exposed (no documented antibiotic exposure during the same period). Cohorts were 1:1 propensity score matched for age, sex, cancer subtype, Charlson comorbidity index, infection-related diagnoses, baseline corticosteroid use, and hospitalization within 30 days prior to ICI initiation. The primary endpoint was OS. Kaplan–Meier and Cox proportional hazards models were used for analysis. Sensitivity analyses evaluated the timing and duration of antibiotic exposure. Results: After matching, 3,024 patients were included (1,512 per cohort). Baseline characteristics were well balanced (mean age 63.7 years; 34% female; median Charlson comorbidity index 5). At a median follow-up of 19.8 months, antibiotic exposure was associated with significantly worse overall survival compared with non-exposure. Median OS was 10.6 months in antibiotic-exposed patients versus 14.3 months in non-exposed patients (log-rank p < 0.001). Antibiotic exposure was independently associated with inferior OS (HR 1.34, 95% CI 1.22–1.47). The negative association was most pronounced among patients with broad-spectrum antibiotic exposure (HR 1.41) and among those with antibiotic exposure within 30 days prior to ICI initiation (HR 1.38). Findings remained robust in sensitivity analyses excluding patients with documented sepsis or prolonged hospitalization. Conclusions: In this large real-world cohort of patients with esophagogastric cancer treated with ICIs, peritreatment antibiotic exposure was associated with significantly worse overall survival. These findings further support the role of the gut microbiome in modulating immunotherapy response and underscore the importance of judicious antibiotic use during ICI therapy.