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Association of Antibiotic Exposure With Survival and Toxicity in Patients With Melanoma Receiving Immunotherapy
Jahan J. Mohiuddin (University of Pennsylvania), Brian K Chu (University of Pennsylvania), Andrea Facciabene (University of Pennsylvania), Kendra Poirier (University of Pennsylvania), Xingmei Wang (University of Pennsylvania), Abigail G. Doucette (Abramson Cancer Center, University of Pennsylvania), Cathy Zheng (Abramson Cancer Center, University of Pennsylvania), Wei Xu (Abramson Cancer Center, University of Pennsylvania), Emily J. Anstadt (University of Pennsylvania), Ravi K. Amaravadi (University of Pennsylvania), Giorgos Constantine Karakousis (University of Pennsylvania), Tara C. Mitchell (University of Pennsylvania), Alexander Chan Chi Huang (University of Pennsylvania), Jacob Ezra Shabason (University of Pennsylvania), Alexander Lin (University of Pennsylvania), Samuel D. Swisher-McClure (University of Pennsylvania), Amit M. Maity (University of Pennsylvania), Lynn Mara Schuchter (University of Pennsylvania), John Nicholas Lukens (University of Pennsylvania)
Résumé : BACKGROUND: Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. METHODS: Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided. RESULTS: There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P <.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR = 2.78, 95% CI = 1.31 to 5.87; P =.007). When limited to only patients who received adjuvant ICI (n = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR = 4.84, 95% CI = 1.09 to 21.50; P =.04). The antibiotic group had a greater incidence of colitis (HR = 2.14, 95% CI = 1.02 to 4.52; P =.046). CONCLUSION: Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.