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

التفاصيل البيبلوغرافية
العنوان:	Association of Antibiotic Exposure With Survival and Toxicity in Patients With Melanoma Receiving Immunotherapy.
المؤلفون:	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.
المصدر:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2021 Feb 01; Vol. 113 (2), pp. 162-170.
نوع المنشور:	Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Oxford University Press Country of Publication: United States NLM ID: 7503089 Publication Model: Print Cited Medium: Internet ISSN: 1460-2105 (Electronic) Linking ISSN: 00278874 NLM ISO Abbreviation: J Natl Cancer Inst Subsets: MEDLINE
أسماء مطبوعة:	Publication: <2003-> : Cary, NC : Oxford University Press Original Publication: Bethesda, Md., U. S. Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health; Washington, for sale by the Supt. of Docs., U. S. Govt. Print. Off.
مواضيع طبية MeSH:	Anti-Bacterial Agents/adverse effects , Gastrointestinal Microbiome/genetics , Genetic Variation/drug effects , Melanoma/drug therapy, Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Agents, Immunological/adverse effects ; Disease-Free Survival ; Female ; Gastrointestinal Microbiome/drug effects ; Genetic Variation/genetics ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immune Checkpoint Inhibitors/adverse effects ; Immunologic Factors/antagonists & inhibitors ; Immunologic Factors/genetics ; Immunotherapy/adverse effects ; Male ; Melanoma/microbiology ; Melanoma/mortality ; Melanoma/pathology ; Middle Aged ; Neoplasm Staging ; Young Adult
مستخلص:	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.)
معلومات مُعتمدة:	P50 CA174523 United States CA NCI NIH HHS; R01 CA219871 United States CA NCI NIH HHS
المشرفين على المادة:	0 (Anti-Bacterial Agents) 0 (Antineoplastic Agents, Immunological) 0 (Immune Checkpoint Inhibitors) 0 (Immunologic Factors)
تواريخ الأحداث:	Date Created: 20200416 Date Completed: 20210618 Latest Revision: 20220831
رمز التحديث:	20240628
مُعرف محوري في PubMed:	PMC7850522
DOI:	10.1093/jnci/djaa057
PMID:	32294209
قاعدة البيانات:	MEDLINE

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تدمد:	1460-2105
DOI:	10.1093/jnci/djaa057