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      Antibiotics impair immune checkpoint inhibitor effectiveness in Hispanic patients with non‐small cell lung cancer (AB‐CLICaP)

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          Abstract

          Background

          The intestinal microbiota is an important factor in modulating immune‐mediated tumor cell destruction. Alterations in the microbiome composition have been linked to reduced efficacy of immune checkpoint inhibitor (ICI) therapies. Therefore, antibiotic treatment (ATB), which modifies the diversity of the gut bacteria populations, could lead to a reduced efficacy of ICI treatments.

          Methods

          This was a retrospective cohort study. Patients with advanced non‐small cell lung cancer (NSCLC) treated with anti‐programmed cell death ligand‐1 (PD‐L1) alone, or in combination in three different countries in Latin America were included. After identification, patients were placed into three groups: Non‐ATB exposed (no‐ATB), exposed within 30 days of the first dose of ICI (pre‐ICI ATB) and patients receiving ATB concomitantly with ICI (ICI‐ATB). Progression‐free survival (PFS), overall survival (OS) and response rates to treatment with ICI were assessed.

          Results

          A total of 140 patients were included, of which 32 patients (23%) received ATB treatment. The most common ATB types were fluoroquinolones and B‐lactams. No differences in survival according to antibiotic type were identified. Median OS in patients not exposed to ATB was 40.6 months (95% CI: 32–67.7), compared with 20.3 months (95% CI: 12.1‐non‐reached [NR]) for patients with pre‐ICI ATB treatment and 24.7 months (95% CI: 13‐NR) for patients treated with ATB concomitantly with ICI. There were no significant differences in terms of PFS, or response rates across all treatment groups.

          Conclusions

          Antibiotic treatment was associated with reduced OS in Hispanic patients with NSCLC treated with ICIs.

          Abstract

          Antibiotic treatment has been shown to deter outcomes in patients treated with immune checkpoint inhibitors. The effect of antibiotics is studied for the first time in Latin American patients undergoing ICI therapy. Patients treated with antibiotics prior or during ICI therapy had a significantly shorter overall survival.

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          Most cited references22

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          Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab

          Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity.
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            Obesity and the human microbiome.

            Ruth E Ley (2010)
            Obesity was once rare, but the last few decades have seen a rapid expansion of the proportion of obese individuals worldwide. Recent work has shown obesity to be associated with a shift in the representation of the dominant phyla of bacteria in the gut, both in humans and animal models. This review summarizes the latest research into the association between microbial ecology and host adiposity, and the mechanisms by which microbes in the gut may mediate host metabolism in the context of obesity. Studies of the effect of excess body fat on the abundances of different bacteria taxa in the gut generally show alterations in the gastrointestinal microbiota, and changes during weight loss. The gastrointestinal microbiota have been shown to impact insulin resistance, inflammation, and adiposity via interactions with epithelial and endocrine cells. Large-scale alterations of the gut microbiota and its microbiome (gene content) are associated with obesity and are responsive to weight loss. Gut microbes can impact host metabolism via signaling pathways in the gut, with effects on inflammation, insulin resistance, and deposition of energy in fat stores. Restoration of the gut microbiota to a healthy state may ameliorate the conditions associated with obesity and help maintain a healthy weight.
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              Antibiotics as deep modulators of gut microbiota: between good and evil.

              The recent increase in our knowledge of human gut microbiota has changed our view on antibiotics. Antibiotics are, indeed, no longer considered only beneficial, but also potentially harmful drugs, as their abuse appears to play a role in the pathogenesis of several disorders associated with microbiota impairment (eg, Clostridium difficile infection or metabolic disorders). Both drug-related factors (such as antibiotic class, timing of exposure or route of administration) and host-related factors appear to influence the alterations of human gut microbiota produced by antibiotics. Nevertheless, antibiotics are nowadays considered a reliable therapy for some non-communicable disorders, including IBS or hepatic encephalopathy. Moreover, some antibiotics can also act positively on gut microbiota, providing a so-called 'eubiotic' effect, by increasing abundance of beneficial bacteria. Therefore, antibiotics appear to change, for better or worse, the nature of several disorders, including IBS, IBD, metabolic disorders or liver disease. This reviews aims to address the potential of antibiotics in the development of major non-communicable disorders associated with the alteration of gut microbiota and on newly discovered therapeutic avenues of antibiotics beyond the cure of infectious diseases.
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                Author and article information

                Contributors
                andres.cardona@clinicadelcountry.com , a_cardonaz@yahoo.com
                ogar@unam.mx
                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                24 July 2020
                September 2020
                : 11
                : 9 ( doiID: 10.1111/tca.v11.9 )
                : 2552-2560
                Affiliations
                [ 1 ] Foundation for Clinical and Applied Cancer Research (FICMAC) Bogotá Colombia
                [ 2 ] Molecular Oncology and Biology Systems Research Group (FOX‐G) Universidad el Bosque Bogotá Colombia
                [ 3 ] Thoracic Oncology Unit Instituto Nacional de Cancerología México City Mexico
                [ 4 ] Clinical and Translational Oncology Group, Clínica del Country Bogotá Colombia
                [ 5 ] Medical Oncology Department Hospital San Juan de Dios San José Costa Rica
                [ 6 ] Thoracic Oncology Department Centro de Investigación y Manejo del Cáncer – CIMCA San José Costa Rica
                [ 7 ] Oncology Department Instituto Nacional de Enfermedades Neoplásicas – IneN Lima Peru
                [ 8 ] Medical Oncology Department, Thoracic Oncology Section Instituto Fleming Buenos Aires Argentina
                [ 9 ] Medical Oncology Department Center for Medical Education and Clinical Research (CEMIC) Buenos Aires Argentina
                [ 10 ] Clinical Oncology Department Clínica Colsanitas Bogotá Colombia
                [ 11 ] Thoracic Oncology Unit Fundación Neumológica Colombiana‐ FNC Bogotá Colombia
                [ 12 ] Oncology Department, Institute of Oncology – ICAL Fundación Santa Fe de Bogotá Bogotá Colombia
                [ 13 ] Thoracic Oncology Unit, Marlene and Stewart Comprehensive Cancer Center University of Maryland Baltimore Maryland USA
                [ 14 ] Institut d'Investigació en Ciències Germans Trias i Pujol Badalona Spain
                [ 15 ] Institut Català d'Oncologia Hospital Germans Trias i Pujol Badalona Spain
                Author notes
                [*] [* ] Correspondence

                Oscar Arrieta, Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Ave San Fernando, Sección XVI, Tlalpan Building 22, Mexico City 14080, Mexico.

                Tel: +52 55 5628 0400

                Fax: +52 55 1315 1223

                Email: ogar@ 123456unam.mx ;

                Andrés F. Cardona, Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia, Foundation for Clinical and Applied Cancer Research – FICMAC, Bogotá, Colombia, Calle 116 No. 9 – 72, c. 318, Bogotá, Colombia.

                Tel: +57 1 6190052

                Fax: +57 1 6190053

                Email: andres.cardona@ 123456clinicadelcountry.com ; a_cardonaz@ 123456yahoo.com

                [†]

                These authors contributed equally to the study.

                [‡]

                Latin American Consortium for the Investigation of Lung Cancer.

                Author information
                https://orcid.org/0000-0003-1274-9273
                https://orcid.org/0000-0003-3525-4126
                Article
                TCA13573
                10.1111/1759-7714.13573
                7471049
                32705787
                d13ddc4a-3d75-4c24-90bb-e5661b5ec821
                © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 28 May 2020
                : 24 June 2020
                : 26 June 2020
                Page count
                Figures: 4, Tables: 2, Pages: 9, Words: 5585
                Funding
                Funded by: Latin American Consortium for Lung Cancer Investigation (CLICaP)
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                September 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.9 mode:remove_FC converted:03.09.2020

                antibiotics,immunotherapy,lung cancer
                antibiotics, immunotherapy, lung cancer

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