Impact of antibiotics on survival outcomes and risk of gastritis/colitis in advanced-stage melanoma patients receiving immune checkpoint inhibitor therapy

To determine the impact of antibiotic spectrum of activity and exposure timing on survival outcomes and development of gastritis/colitis. We conducted a single-center, retrospective cohort study of 214 patients with advanced, metastatic, or unresectable melanoma treated with immune checkpoint inhibitors. Antibiotic exposure was classified by spectrum of activity (with and without anaerobic coverage) and antibiotic timing. Primary outcomes were the effect of antibiotic administration 30-days prior to starting ICI therapy and during ICI therapy on overall survival (OS) and progression-free survival (PFS). Antibiotic exposure during ICI was associated with improved OS (HR: 0.57, 95% CI (0.35–0.92), p = 0.023). Use of antibiotics without anaerobic coverage was associated with improved PFS (HR: 0.53, 95% CI (0.32–0.87), p = 0.013), and OS (HR: 0.47, 95% CI (0.24–0.92), p = 0.026). There was a trend toward increased risk of gastritis/colitis with antibiotics without anaerobic coverage during ICI therapy, although this did not reach statistical significance (OR 2.08, 95% CI (0.43–5.46), p = 0.069). Antibiotic timing and spectrum of activity may be predictive of survival outcomes and risk of developing gastritis/colitis in ICI-treated patients with advanced-stage melanoma. Unlike previous studies, we found improved survival in patients receiving antibiotics during treatment and in those receiving antibiotics without anaerobic coverage. This study is set out to answer a focused question: How do the timing of antibiotics (before vs during immunotherapy) and the kind of antibiotics used (with or without “anaerobic” coverage) relate to patient survival and to the risk of treatment-related stomach or bowel inflammation (gastritis/colitis)? We reviewed records from 214 people with advanced-stage melanoma who received immune checkpoint inhibitors (ICIs), medicines that help the immune system combat cancer. We grouped antibiotic use by when it was given, within 30 days before starting ICI or during ICI therapy, and by what was given (antibiotics that do versus do not target anaerobic bacteria). From this study we found that patients who needed antibiotics during ICI tended to live longer than those who did not receive antibiotics during treatment, even after accounting for key clinical differences. By contrast, antibiotics before starting ICI showed a tendency toward worse survival. Among antibiotics given during ICI, regimens without anaerobic coverage were linked to better cancer outcomes than other regimens. Since this was a single-center, retrospective study, it cannot prove cause and effect and may miss outside prescriptions or other confounders. Still, the results suggest that when antibiotics are given and which ones are chosen could matter during immunotherapy, supporting careful antibiotic stewardship and the need for larger prospective studies.