Association between antibiotic use, immune-related adverse events, and efficacy of immunotherapy in esophageal squamous cell carcinoma

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are essential for treating esophageal squamous cell carcinoma (ESCC). As antibiotics (Abx) may reduce ICI efficacy, and immune-related adverse events (irAEs) relate to better outcomes, we investigated their association. PATIENTS AND METHODS: We retrospectively analyzed 121 advanced or metastatic ESCC patients treated with ICIs, assessing outcomes based on Abx use and irAEs. RESULTS: Forty-one patients (33.9%) were in the Abx (+) group, showing a significantly shorter median progression-free survival (PFS) (2.5 vs. 6.5 months; p = 0.029) and lower disease control rate (36.8% vs. 60.9%; p = 0.0145) than those in the Abx (-) group. irAEs were less frequent in the Abx (+) group (29.3% vs. 58.8%; p = 0.0037). The positive impact of irAEs on ICI efficacy was significant in overall population [irAE(-) vs. irAE(+): PFS, 4.4 months (95% CI 2.5-5.3) vs. 8.8 months (95% CI 5.9-13.7); log-rank p = 0.001; Hazard ratio (HR) 1.76, 95% CI 1.14-2.74; p = 0.011; overall survival (OS), 10.6 months (95% CI 7.0-13.1) vs. 18.1 months (95% CI 9.2-25.9); log-rank p = 0.043; HR 1.61, 95% CI 1.01-2.55; p = 0.046] but diminished if received Abx. Notably, the Abx (-)/irAE (+) group had the best outcomes, while the Abx (+)/irAE (-) group had the worst PFS (8.7 vs. 2.4 months; HR 2.07; p = 0.011) and OS (18.1 and 6.8 months; HR 1.89; p = 0.036). CONCLUSION: Antibiotic use was linked to reduced ICI efficacy and fewer irAEs, suggesting impaired immune activation in ESCC patients.