The role of durvalumab in the treatment of biliary tract tumors

Abstract

Malignant biliary tract tumors are highly aggressive, with a 5-year survival rate in advanced disease 2–7%. During last decade therapeutic options for treatment biliary cancer were extremely limited. The unchanged standard of first-line therapy since 2010, based on ABC-02 trial, has been GemCis combination. The TOPAZ-1 phase III trial for the first time for last 12 years reported a survival benefit with the antiprogrammed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer, achieving a median survival of 12.9 months (11.6–14.1) compared to 11.3 months (10.1–12.5) in the placebo group (RR 0.76 [0.64–0.91]). The objective response rate was 26.7% in the durvaulmab group compared with 18.7% in the placebo group. Median of overall survival is highly dependent on the best antitumor response achieved, with patients in the durvalumab group with a partial/complete response having a median survival of 19.5 months (95% CI: 15.7–28.3), with stable disease 13.6 months (95% CI: 12.2–14.7), and with progression disease 5.7 months (95% CI: 3.6–8.9). This article describes the features of the tumor microenvironment and immunogenicity of cholangiocarcinomas, provides studies of the early phases of immunotherapy with durvalumab and tremelimumabm, and provides a detailed analysis of the key study TOPAZ-1. In addition, we describe a clinical case that demonstrates long-term disease of advanced cholagiocarcinoma due to impact of significant advances in the modern treatment of cholangiocarcinoma with the introduction of immunotherapy with durvalumab, targeted therapy and the use of a new technique of local radioembolization.