Association of Antibiotic Exposure With Survival and Toxicity in Patients With Melanoma Receiving Immunotherapy.

Autor:	Mohiuddin JJ; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Chu B; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Facciabene A; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Poirier K; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Wang X; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA., Doucette A; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Zheng C; Tara Miller Melanoma Center, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Xu W; Tara Miller Melanoma Center, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Anstadt EJ; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Amaravadi RK; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Karakousis GC; Division of Endocrine and Oncologic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA., Mitchell TC; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Huang AC; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Shabason JE; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Lin A; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Swisher-McClure S; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Maity A; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Schuchter LM; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lukens JN; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2021 Feb 01; Vol. 113 (2), pp. 162-170.
DOI:	10.1093/jnci/djaa057
Abstrakt:	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. (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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