Abstract

BackgroundThe use of antibiotics is known to alter the gut microbiome and it is hypothesised that the use of antibiotics may also alter the response to immune checkpoint inhibitors (ICI). As data is limited from real-world settings, we performed a retrospective audit of patients who received ICI along with concomitant antibiotics.Patients and MethodsThis study is a retrospective audit of a prospectively collected the database of patients who received ICI for advanced solid tumours in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. Antibiotic use was recorded from 2 weeks before the start of ICI and concomitantly with ICI. All statistical calculations were performed using Statistical Package for the Social Sciences (SPSS) statistical software for windows version 20.0.ResultsA total of 155 patients were identified as having received ICI during the study period, out of which 70 (44%) patients received antibiotics. Median PFS in patients who received antibiotics was 1.7 months (95% CI: 1.1–2.3) as against 3.6 months (95% CI: 2.3–4.8) for patients who did not receive antibiotics (p = 0.912). Median OS in the patients who received antibiotics was 3.9 months (95% CI: 1.8–11.4) as compared to 9.2 months (95% CI: 4.2–12.3) who did not receive antibiotics p = 0.053 (HR = 1.023; 95% CI: 1.00–1.04). Among the patients who received antibiotics, median OS for patients who received ≤10 days of antibiotics was 8.8 months (95% CI: 4.2–11.2) while for patients receiving >10 days of antibiotics, it was 2.8 months (95% CI: 1.2–4.4), p = 0.025 (HR = 2.0, 95% CI: 1.1–3.7). Thirty-three (21.2% of total) patients received antibiotics during the window of 2 weeks before the start of ICI to 2 months of starting ICI. Median OS in the patients who received antibiotics in this window was 2.8 months (95% CI: 1.2–4.5) as compared to 9.2 months (95% CI: 5.2–13.1) who did not receive antibiotics p = 0.008 (HR = 1.8; 95%CI: 1.2–3.0).ConclusionsThis study shows that the judicious use of antibiotics is required in patients on ICI or scheduled to be started on ICI.

Highlights

  • The human gut microbiota represents a complex and interconnected ecosystem composed of trillions of microorganisms living within the human gut [1]

  • Median progression free survival (PFS) in patients who received antibiotics was 1.7 months as against 3.6 months for patients who did not receive antibiotics (p = 0.912)

  • This study shows that the judicious use of antibiotics is required in patients on immune checkpoint inhibitors (ICI) or scheduled to be started on ICI

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Summary

Introduction

The human gut microbiota represents a complex and interconnected ecosystem composed of trillions of microorganisms living within the human gut [1]. In a study by Derosa et al [3], a negative association of antibiotics was observed on the clinical activity of ICI in patients with advanced renal and non-small-cell lung cancer both in terms of progression free survival (PFS) and overall survival (OS) [3]. Gopalkrishnan et al [4] prospectively studied patients with metastatic melanoma treated with ICI and classified patients as responders if they achieved at least disease stability for 6 months. They found significant differences in the composition of bacterial flora between responders and non-responders. The use of antibiotics is known to alter the gut microbiome and it is hypothesised that the use of antibiotics may alter the response to immune checkpoint inhibitors (ICI). As data is limited from real-world settings, we performed a retrospective audit of patients who received ICI along with concomitant antibiotics

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