Effects of concomitant gut-microbiome altering medications on immune checkpoint inhibitors therapy: A retrospective study

6617 Background: In cancer patients, gut microbiota influences the antitumor immune response, efficacy, and safety of immune checkpoint inhibitors (ICIs). Antibiotics (ATBs), proton pump inhibitors (PPIs), and corticosteroids can alter the distribution of gut microbiota, resulting in dysbiosis, which can potentially reduce the efficacy of ICIs and may contribute to increased incidence of immune-related adverse effects (irAEs). Methods: We conducted a retrospective observational study to investigate the influence of concurrent medicines on patients receiving ICIs at the University of Vermont Cancer Center. We examined the medical records of people who received ICIs alone or in combination with chemotherapy or targeted therapy as a first-line therapy between January 2017 and June 2022. Patients who got ATBs, PPIs, and corticosteroids (>10 mg prednisone) one month before commencing ICIs and during the first six months of treatment were compared to those who did not. We looked at the relative risk for overall survival and the occurrence of irAEs in both cohorts. Results: We identified 266 patients, of which 99 (37%) have died. The mean age was 64 years, 55% were male, and 97% of the patients were White. Lung cancer was the most commonly identified malignancy at 36%, and 55% of the cancers were stage IV. The median ECOG was 1, and the median Charlson morbidity index was 6. Of the total cohort, 62% received antibiotics, 67% received steroids, 45% received PPIs, 31% received two of the three, and 27% received all three. The relative risk (RR) of death in the cohort which received antibiotics was 1.53 (p = 0.02), the cohort which received steroids was 1.73 (p = 0.006), and the cohort that received PPIs was 1.61 (p = 0.006). For the group that received two or all three medications, the RR was 2.18 (p = 0.003). Regarding irAEs, the group that received steroids had a RR of 2.13 (p = 0.07); however, most of these patients likely received steroids for an irAE. Antibiotics and PPIs were not associated with a higher risk of irAEs. One of the significant limitations of our study is the small sample size and the retrospective data collection. Data is also confounded because it includes patients who have received ICIs in combination with chemotherapy or other agents. Conclusions: Our study suggests that patients who received any of the gut microbiome-modifying medications before starting and within the early phase of ICIs treatments are at higher risk of mortality, likely owing to the poor efficacy of ICIs or possibly because these patients are sicker at baseline. However, we must be judicious with using such medications when patients undergo treatment with ICIs. Large prospective studies looking at this association are needed to understand the risk and potential outcomes. [Table: see text]