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Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice

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Purpose Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of… Click to show full abstract

Purpose Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. Materials and methods A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan–Meier method, was performed, and association with various independent variables was assessed using Cox regression. Results We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P  < .0001), antibiotics (7 vs. 15 months, P  < .017), anxiolytic drugs (8 vs. 16 months, P  < .015), and corticosteroids (6 vs. 19 months, P  < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07–3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77–9.92; P  < .001). Conclusion Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Keywords: intestinal dysbiosis; immune checkpoint; dysbiosis related; dysbiosis; checkpoint inhibitors; related drugs

Journal Title: Clinical and Translational Oncology
Year Published: 2020

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