Impact of Antibiotic Therapy in Patients with Cholangiocarcinoma Treated with Chemoimmunotherapy

Introduction: Patients with biliary tract cancers (BTCs) often require antibiotic therapy before starting systemic treatment that includes an immune checkpoint inhibitor. This study aimed to evaluate the prognostic impact of antibiotic therapy administered in the 15 days prior to the start of chemoimmunotherapy in patients with BTC. Methods: The study population included patients with metastatic or locally advanced BTC from Western and Eastern populations treated with first-line chemoimmunotherapy. The aim of the study was to evaluate the impact of antibiotic therapy in the 15 days prior to starting oncological treatment (AT population) compared to patients who did not receive antibiotic therapy (NAT). Univariate and multivariate analyses were used to evaluate predictive factors for overall survival (OS) and progression-free survival (PFS), while prognostic factors were analyzed by univariate and multivariate analysis using Cox regression model. Results: A total of 666 patients were enrolled in the study: 93 (14%) in AT cohort and 573 (86%) in NAT cohort. In the AT population, the incidence of cholangitis (p = 0.0017), alanine aminotransferase elevation (p = 0.0009), fever (p = 0.0021), decreased appetite (p = 0.0007), itching (p = 0.0081), and rash (p = 0.012) was significantly higher compared to the NAT. The median OS was 15.9 months (95% confidence interval [CI]: 13.8-18.3) in NAT cohort versus 10.1 months (95% CI: 7.9-12.4) in AT cohort (NAT vs. AT, hazard ratio [HR]: 0.43, 95% CI: 0.27-0.70, p = 0.0006), while median PFS was 8.5 months in NAT cohort versus 5.4 months in AT cohort (NAT vs. AT, HR: 0.49, 95% CI: 0.34-0.71, p = 0.0001). Multivariate analysis confirmed the prognostic role of antibiotic for OS and PFS. Finally, NAT cohort showed better overall response rate compared with AT cohort (31.4% vs. 20.4%, p = 0.03). Conclusions: The use of antibiotic therapy in the 15 days prior to starting chemoimmunotherapy is an independent unfavorable prognostic factor for survival in our cohort of patients with advanced BTC treated with cisplatin, gemcitabine and durvalumab.