Real-Practice Analysis of Potential Antibiotic Interactions in Patients Treated With Immune Checkpoint Inhibitors: An Observational Study From an Italian Referral Cancer Center

Abstract

Purpose: Inappropriate use of antibiotics contributes to the increase in antimicrobial resistance with negative health safety implications. Global health organizations have promoted projects to improve proper and rational use of antibiotics. Recent studies show how antibiotics can also influence the efficacy of immune checkpoint inhibitors (ICIs) treatment in cancer patients. This work analyzes the impact of concomitant antibiotic therapy in patients affected by skin, lung, and kidney cancer, who started immunotherapy in 2020-2021 at Veneto Institute of Oncology IRCCS. The aim of this study is to evaluate clinical outcomes, treatment efficacy, discontinuation causes, and occurrence of adverse drug reactions in cancer patients treated with ICIs.

Methods: Data from the real-world retrospective study were extracted from Territorial Pharmaceutical Care databases, medical records, and the AIFA registry. A descriptive analysis of the study population was performed, as well as of patient outcomes in terms of progression-free survival (PFS) and overall survival (OS).

Results: A total of 239 subjects affected by kidney (8%), lung (48%), and skin (44%) cancer were enrolled; of these, 50%, 32%, 9%, and 9% were treated with single-agent nivolumab, pembrolizumab, atezolizumab, and cemiplimab, respectively. A total of 119 patients received concomitant antibiotic therapy. Median OS was 8.8 months (95% CI: 5.02–11.8) and 31.05 months (95% CI: 24.81–NA) in subjects with high and low antibiotic exposure, respectively. Multivariate subgroup analysis confirmed that high antibiotic exposure is an unfavorable factor also for median PFS.

Conclusion: A prolonged exposure to antibiotics correlates with unfavorable outcomes in cancer patients undergoing concomitant immunotherapy. Thus, managing antibiotic exposure is fundamental for optimizing ICI treatment.