Review

Moving beyond single-agent checkpoint inhibition in biliary tract cancers: what is the next frontier?

https://orcid.org/0000-0001-6122-1374

Center for Personalized Medicine, Hospital Israelita Albert Einstein, Sao Paulo, 05652-900, Brazil

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Tanios Bekaii-Saab

*Author for correspondence:

E-mail Address: bekaii-saab.tanios@mayo.edu

Mayo Clinic Comprehensive Cancer Center, Phoenix, AZ 85054, USA

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Published Online:25 Apr 2023https://doi.org/10.2217/imt-2022-0201

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Abstract

Background: Immunotherapy has been shown to improve outcomes for patients with cancer. Biliary tract cancers are a group of lethal diseases, and immunotherapy is an exciting new strategy to treat patients in advanced stages. Role of immunotherapy in biliary cancers: Durvalumab, an anti-PD-L1 antibody, is a new immunotherapy option for patients with advanced biliary cancers. In a randomized phase III trial, the combination of durvalumab and chemotherapy improved disease outcomes, including overall survival, in patients with advanced biliary cancers regardless of PD-L1 expression. Future perspective: Promising new combinations with new and potent antibodies or antiangiogenics are under development. Combinations with new immunotherapy agents targeting CTLA-4 or OX40 can enhance T-cell activation and improve outcomes compared with single anti-PD-1/PD-L1 agents. Furthermore, ctDNA is being used as an alternative to tissue genomic analysis and can be used to identify actionable targets. In this review, we will discuss the most important studies involving immunotherapy in biliary cancers as well as future perspectives in the field.

Plain language summary

New treatment strategies for advanced biliary cancers with chemoimmunotherapy combinations have been shown to lead to better tumor responses and overall survival compared with chemotherapy alone. The combination of durvalumab, cisplatin and gemcitabine may become a new standard of care for advanced disease despite the modest improvement in median overall survival of less than 2 months. Promising combinations with anti-CTLA-4 antibodies or antiangiogenics are underway with the objective of improvement in survival. Although multiple combinations are available with the potential to establish a new standard of care, concerns regarding toxicities should also be evaluated. In this review, we will discuss the most important studies involving immunotherapy in biliary cancers as well as future perspectives in the field.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 7

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History

Received 6 August 2022

Accepted 16 March 2023

Published online 25 April 2023

Published in print May 2023

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Author contributions

T Bekaii-Saab and PLS Uson Junior performed the literature review, collected all data and wrote the manuscript. Both authors have read and approved the final manuscript.

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

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