Recent advances of immunotherapy for biliary tract cancer

ABSTRACT

Introduction: Biliary tract cancer (BTC) is a heterogeneous group of aggressive malignancies comprising intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. Although recent years have witnessed the emergence of novel treatment targets, medical therapy remains a compelling challenge in these hepatobiliary malignancies. In order to provide more effective treatment options, immune checkpoint inhibitors (ICIs) are currently under investigation in advanced BTC, with controversial results reported so far.

Areas covered: This review provides an overview regarding current scenario of ICIs and immune-based combinations in advanced BTC, where several novel treatments are currently being developed, some of which have suggested interesting efficacy in recent clinical trials. In addition, we provide a report of ongoing Phase I to III clinical trials assessing ICIs and new immunotherapeutic strategies for advanced BTC.

Expert opinion: Although immunotherapy has revolutionized the treatment landscape of several hematological and solid tumors, the role of ICIs and immune-based combinations in advanced BTC is still unclear. Despite ICI monotherapy has reported limited efficacy in this setting, the durable responses observed in sporadic cases suggest that testing patients for MMR, MSI, TMB, and PD-L1 expression is warranted. Results of currently ongoing trials are highly awaited.

KEYWORDS:

• Biliary tract cancer
• immunotherapy
• cholangiocarcinoma
• pembrolizumab
• nivolumab

Article highlights

• Cholangiocarcinoma (CCA) is a rare malignancy with overall poor prognosis.

• There are limited options regarding systemic treatment for CCA, with combination chemotherapy regimens achieving limited responses so far.

• In the past few years, immunotherapy has revolutionized the treatment landscape of several hematologic and solid tumors.

• Single-agent immune checkpoint inhibitors have reported controversial results in CCA, suggesting modest but real responses in a limited subset of patients.

• Novel combination strategies with immune checkpoint inhibitors are currently being explored in this setting, with a view to provide more effective treatment options in advanced CCA.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.