Novel treatments for advanced cholangiocarcinoma

Abstract

Cholangiocarcinoma (intrahepatic, hilar or extrahepatic [distal bile duct]) is an aggressive malignancy with unmet treatment needs in the advanced setting. The current first-line standard of care for patients with locally advanced or metastatic biliary tract cancer is the combination of cisplatin and gemcitabine chemotherapy. The median overall survival for these patients is less than 1 year, and novel treatment approaches are mandated. Locoregional therapy such as chemosaturation, chemoembolisation, ablation and radiation-based approaches have been assessed in small, early phase trials and retrospective series and show some promise in local control and overall survival in the locally advanced and palliative setting, but results of prospective randomised trials will evaluate the magnitude of benefit compared to currently available options. Novel therapy clinical trials targeting the isocitrate dehydrogenase 1 and fibroblast growth factor receptor 2 fusion mutations are ongoing, and the use of immune checkpoint inhibitors in this disease is being investigated. A greater understanding of cholangiocarcinoma biology, its oncogenic landscape and complex interaction with the tumour microenvironment and immune response is imperative to optimise patient’s quality of life and survival.