Immune checkpoint inhibitor therapy in biliary tract cancer (cholangiocarcinoma)

Biliary tract cancer (BTC) is a rare malignancy with overall poor prognosis. There are limited options regarding systemic therapy for this disease and historically only multi-agent chemotherapy regimens achieve meaningful responses that are often short lived. In the past several years immune checkpoint inhibitor (ICI) therapy has been established as an effective systemic therapy option in many solid tumors. The BTC tumor microenvironment (TME) including immune cells (T cells, macrophages, dendritic cells and natural killer cells) and immune checkpoint expression has been characterized. Findings have clinical implications that suggest that this entity is potentially amenable to immunomodulation, including via checkpoint inhibition. Single agent ICI studies have only been reported in the past few years and have mostly targeted the checkpoints PD-1 and PD-L1. As in other tumor subtypes patients with rare mismatch repair deficiency or microsatellite instability appear to have exquisite sensitivity to checkpoint inhibition. Abstracts and published studies suggest modest but real responses in all subtypes including objective response rates (ORRs) in the 5-20% range and meaningful disease control. They have paved the way for novel combination trials featuring a variety of treatment strategies and agents that look to enhance ICI efficacy and create long-term responders.