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    Cumulative antibiotic use significantly decreases efficacy of checkpoint inhibitors in patients with advanced cancer

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    Authors
    Tinsley, Nadina
    Zhou, Cong
    Tan, Grace
    Rack, Samuel
    Lorigan, Paul C
    Blackhall, Fiona H
    Krebs, Matthew G
    Carter, Louise
    Thistlethwaite, Fiona C
    Graham, Donna
    Cook, Natalie
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    Affiliation
    The Christie NHS Foundation Trust, Manchester
    Issue Date
    2019
    
    Metadata
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    Abstract
    BACKGROUND: With the advent of immunotherapy, substantial progress has been made in improving outcomes for patients with advanced cancer. However, not all patients benefit equally from treatment, and confounding immune-related issues may have an impact. Several studies suggest that antibiotic use (which alters the gut microbiome) may result in poorer outcomes for patients treated with immune checkpoint inhibitors (ICI). MATERIALS AND METHODS: This is a large, single-site retrospective review of n = 291 patients with advanced cancer treated with ICI (n = 179 melanoma, n = 64 non-small cell lung cancer, and n = 48 renal cell carcinoma). Antibiotic use (both single and multiple courses/prolonged use) during the periods 2 weeks before and 6 weeks after ICI treatment was investigated. RESULTS: Within this cohort, 92 patients (32%) received antibiotics. Patients who did not require antibiotics had the longest median progression-free survival (PFS), of 6.3 months, and longest median overall survival (OS), of 21.7 monthS With other clinically relevant factors controlled, patients who received a single course of antibiotics had a shorter median OS (median OS, 17.7 months; p = .294), and patients who received multiple courses or prolonged antibiotic treatment had the worst outcomes overall (median OS, 6.3 months; p = .009). Progression-free survival times were similarly affected. CONCLUSION: This large, multivariate analysis demonstrated that antibiotic use is an independent negative predictor of PFS and OS in patients with advanced cancer treated with ICIS This study highlighted worse treatment outcomes from patients with cumulative (multiple or prolonged courses) antibiotic use, which warrants further investigation and may subsequently inform clinical practice guidelines advocating careful use of antibiotics IMPLICATIONS FOR PRACTICE: Antibiotic use is negatively associated with treatment outcomes of immune checkpoint inhibitors (ICI) in advanced cancer. Cumulative antibiotic use is associated with a marked negative survival outcome. Judicious antibiotic prescribing is warranted in patients receiving treatment with ICI for treatment of advanced malignancy.
    Citation
    Tinsley N, Zhou C, Tan G, Rack S, Lorigan P, Blackhall F, et al. Cumulative antibiotic use significantly decreases efficacy of checkpoint inhibitors in patients with advanced cancer. Oncologist. 2019.
    Journal
    Oncologist
    URI
    http://hdl.handle.net/10541/622006
    DOI
    10.1634/theoncologist.2019-0160
    PubMed ID
    31292268
    Additional Links
    https://dx.doi.org/10.1634/theoncologist.2019-0160
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1634/theoncologist.2019-0160
    Scopus Count
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