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Résumé : Background Antibiotic exposure has been hypothesized to reduce the efficacy of immune checkpoint inhibitors (ICIs) through disruption of the gut microbiome. 1 However, published data remains inconsistent, and the impact of antibiotic use during active ICI treatment on clinical outcomes and immune-related adverse events (irAEs) remains incompletely understood.2 Data from the Middle East and North Africa (MENA) region are scarce. We evaluated the association between antibiotic exposure during ICI therapy and treatment outcomes in patients with solid tumors treated at a tertiary academic cancer center.Methods We conducted a retrospective cohort study of adult patients with solid tumors treated with ICIs at the American University of Beirut Medical Center, Lebanon. Patients were categorized according to antibiotic exposure during ICI therapy. Primary outcomes were objective response rate (ORR), any immune-related adverse event (irAE), and grade ≥2 irAE. Secondary outcomes were overall survival (OS) and progression-free survival (PFS). Multivariable logistic and Cox regression models adjusted for demographic, disease, and treatment-related confounders. A 90-day landmark analysis assessed potential survivor bias. Secondary analyses examined antibiotic route, spectrum, duration, and number of courses among exposed patients.Results Among 700 patients treated with ICIs, 265 (37.9%) received antibiotics during treatment ( table 1). Antibiotic exposure was associated with significantly higher odds of objective response (aOR 1.75, 95% CI 1.10–2.81; p = 0.018), any irAE (aOR 1.60, 95% CI 1.11–2.31; p = 0.011), and grade ≥2 irAEs (aOR 1.64, 95% CI 1.11–2.41; p = 0.012). In contrast, antibiotic exposure was not associated with inferior survival outcomes, with no significant effect observed for PFS (aHR 1.04, 95% CI 0.70–1.53; p = 0.861) and no evidence of worse OS (aHR 0.67, 95% CI 0.45–1.01; p = 0.056). Findings were consistent in the 90-day landmark analysis. Among antibiotic-exposed patients, broad-spectrum combination therapy was associated with increased odds of any irAE (aOR 1.94, 95% CI 1.05–3.60; p = 0.035). Compared with antibiotic exposure for 1–7 days, treatment durations of 8–30 days and >30 days were associated with progressively higher risks of both any irAE and grade ≥2 irAEs. Neither antibiotic route nor exposure characteristics significantly influenced OS or PFS.Conclusions Contrary to prevailing concerns regarding microbiome disruption and reduced immunotherapy efficacy, antibiotic exposure during ICI treatment was associated with improved objective response and increased immune-related toxicity without adversely affecting survival. Broad-spectrum and prolonged antibiotic exposure appeared to drive the increased risk of irAEs. These findings challenge the assumption that antibiotic use uniformly impairs immunotherapy outcomes and warrant prospective validation.References Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018 Jan 5;359(6371):91–97.Crespin A, Le Bescop C, de Gunzburg J, Vitry F, Zalcman G, Cervesi J, Bandinelli PA. A systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of cancer patients treated with immune checkpoint inhibitors. Front Oncol. 2023 Mar 2;13:1075593.Ethics Approval The study was approved by the Institutional Review Board of the American University of Beirut (IRB ID: BIO-2024-0295). The requirement for informed consent was waived owing to the retrospective nature of the study.Abstract 367 Table 1