Antibiotic therapy and outcomes with gemcitabine, cisplatin and durvalumab in advanced cholangiocarcinoma: A large real-world analysis.

Abstract

815 Background: Antibiotic exposure within close proximity to the initiation of systemic chemoimmunotherapy often occurs in patients diagnosed with cholangiocarcinoma (CCA). However, the data regarding the clinical impact of antibiotic exposure on outcomes are conflicting and limited. We sought to evaluate the impact of antibiotic therapy with chemoimmunotherapy in a large real-world cohort of patients with CCA. Methods: We conducted a retrospective analysis using the TriNetX database using ICD-10 codes to identify patients diagnosed with advanced CCA who received therapy with Gemcitabine, Cisplatin and Durvalumab. These patients were further stratified into two cohorts: those who received oral or intravenous antibiotic therapy in 15 days leading up to or 15 days after initiation of chemoimmunotherapy versus those who did not. Baseline characteristics were compared between the two cohorts. Survival outcomes were assessed using Kaplan-Meier survival analysis. A p-value of <0.05 was considered statistically significant. Results: A total of 2,348 patients were included in the analysis, of which, 1,063 (45.3%) received antibiotic therapy. The groups that did and did not receive antibiotic therapy were similar based on median age (66.8 vs 67.3 years, p=0.23), sex (males 50% vs 48%, p=0.21) and race composition (White patients 67% vs 65%, p=0.45). However, as expected, patients who received antibiotic therapy had a higher prevalence of febrile events (25.4% vs 18.6%, p=0.0005) and cholangitis (15.2% vs 9.0%, p<0.0001). Rates of transaminitis were similar between the two cohorts (10.8% vs. 9.2%, p=0.24). Patients who received antibiotic therapy were noted to have a statistically significant shorter median survival of 13.3 months vs 15.2 months (log-rank p=0.0204; Hazard ratio [HR] 1.156, 95% CI 1.02–1.31). Conclusions: In this large real-world analysis, antibiotic exposure within the peri-treatment window of chemoimmunotherapy in advanced CCA was associated with inferior survival outcomes. These differences may reflect the impact of antibiotic therapy on the gut and tumor microbiome, potentially altering host–tumor–immune interactions and therapeutic efficacy. Prospective, microbiome-focused studies are warranted to characterize specific microbial alterations and elucidate the mechanistic basis underlying these observations.