Review

*Author for correspondence:

Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, M20 4BX, UK

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Kathryn Graham

The Library, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK

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Jack Gleeson

https://orcid.org/0000-0001-6908-495X

Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, M20 4BX, UK

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Richard A Hubner

Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, M20 4BX, UK

Division of Cancer Sciences, University of Manchester, Manchester, M13 9PL, UK

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Juan W Valle

Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, M20 4BX, UK

Division of Cancer Sciences, University of Manchester, Manchester, M13 9PL, UK

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Mairéad G McNamara

**Author for correspondence:

E-mail Address: mairead.mcnamara@nhs.net

Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, M20 4BX, UK

Division of Cancer Sciences, University of Manchester, Manchester, M13 9PL, UK

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Published Online:3 Apr 2023https://doi.org/10.2217/imt-2022-0190

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Abstract

There is a critical need for novel therapies to treat patients with advanced biliary tract cancer (BTC). This systematic review summarizes the evidence-based knowledge for the potential role of PD-1 and PD-L1 monoclonal antibodies in the treatment of patients with early-stage and advanced BTC. An Embase database search was conducted, identifying 15 eligible phase II/III clinical trials for review. Results from recent phase III trials show a statistically significant overall survival (OS) benefit from the addition of PD-1/PD-L1 inhibitors to chemotherapy in the first-line management of advanced BTC. Future research should concentrate on the discovery of biomarkers to identify patients who would benefit most from these therapies.

Plain language summary

The majority of patients with biliary tract cancer (BTC) present with advanced disease (disease that has spread) that cannot be cured. The current mainstay of treatment for advanced BTC is chemotherapy, which aims to prolong life expectancy to just under 12 months. The need for new, more effective treatments for advanced BTC is crucial. This systematic review summarizes the most recent clinical trials that have tested the use of newer drugs called immunotherapy (PD-1 and PD-L1 monoclonal antibodies) in the treatment of both early-stage and advanced BTC. Fifteen clinical trials have been included, each testing different immunotherapy drugs either alone or in combination with other anti-cancer treatments. Promising results from larger trials, have given hope for longer survival in patients with advanced BTC when treated with immunotherapy plus chemotherapy as their first-line treatment after diagnosis. However, further investigation is required to determine whether certain patients might benefit more than others and if immunotherapy drugs can also be given to patients at an earlier or later stage of their disease.

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Review of phase III clinical trials reveals that the addition of immunotherapy to chemotherapy can improve survival of patients with advanced biliary tract cancer. #immunotherapy #cancerresearch

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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 29 July 2022

Accepted 7 March 2023

Published online 3 April 2023

Published in print May 2023

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Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/imt-2022-0190

Author contributions

K Graham performed the initial database search. RD Mahmood and MG McNamara developed the initial concept of the manuscript. RD Mahmood drafted and revised the manuscript. MG McNamara reviewed and approved the draft and final version of the manuscript. All authors approved the final version of the manuscript.

Financial & competing interests disclosure

RA Hubner has served on the advisory board for Roche, BMS, Eisai, Celgene, Beigene, Ipsen and BTG. He has received speaker fees from Eisai, Ipsen, Mylan and PrimeOncology and has received travel and educational support from Bayer, BMS and Roche, all outside of the scope of this work. JW Valle has served in consulting or advisory roles for Agios, AstraZeneca, Delcath Systems, Keocyt, Genoscience Pharma, Incyte, Ipsen, Merck, Mundipharma EDO, Novartis, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED and Wren Laboratories; served on speakers' bureaus for Imaging Equipment Limited, Ipsen, Novartis and Nucana; and received travel grants from Celgene and Nucana, all outside of the scope of this work. MG McNamara received research grant support from Servier, Ipsen and NuCana. She has received travel and accommodation support from Bayer and Ipsen and speaker honoraria from Pfizer, Ipsen, NuCana, Mylan and AAA. She has served on advisory boards for Celgene, Ipsen, Sirtex, Baxalta, Incyte and Astra Zeneca, all outside scope of this work. The authors have no other 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 apart from those disclosed.

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

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Targeting PD-1/PD-L1 in biliary tract cancer: role and available data

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References