Impact of Antibiotic Therapy in Patients with Cholangiocarcinoma Treated with Chemoimmunotherapy

BACKGROUND: Patients with biliary tract cancers (BTC) often require antibiotic therapy before starting systemic treatment that includes an immune checkpoint inhibitor. This study aims to evaluate the prognostic impact of antibiotic therapy administered in the 15 days prior to the start of chemoimmunotherapy in patients with BTC. MATERIAL AND 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 is 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: 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), ALT 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% CI 13.8 - 18.3) in NAT cohort vs 10.1 months (95% CI 7.9 - 12.4) in AT cohort (NAT vs AT, HR 0.43,95% CI 0.27 - 0.70-15.6 p=0.0006) while median PFS was 8.5 months in NAT cohort vs 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.