The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers.

Andrea Casadei-Gardini, Gianluca Masi, Lorenza Rimassa, David James Pinato, Giuseppe Cabibbo, Bruno Daniele, Angela Lamarca

Journal: Cancer treatment reviews 2025;137():102955

PMID: 40373702

Abstract

Hepatobiliary malignancies encompass a spectrum of invasive carcinomas arising in the liver [hepatocellular carcinoma (HCC), bile ducts [intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (EHC)] and the gallbladder. These malignancies represent a growing global health burden, with rising incidence and mortality rates and their overall prognosis remains poor because many patients present with advanced unresectable disease at diagnosis. In recent years, significant advancements in understanding HCC immunogenicity have reshaped the therapeutic scenario of advanced HCC with the immunotherapy revolutionizing the current HCC treatment landscape and patients' prognosis. Moreover, the addition of immunotherapy to chemotherapy has recently established a new standard of care first-line treatment for patients with biliary tract cancers (BTCs) who had historically few therapeutic options. Currently, immunotherapy and immune checkpoint inhibitor (ICI)-based regimens stand as a valuable and practice-changing options in both HCC and BTC management. The mounting recent evidence supporting immunotherapy's survival benefit demands clinicians to stay updated with a rapidly evolving treatment landscape as well as gain knowledge about patient selection, response rate compared with other systemic treatments and immune-mediated adverse events (imAEs) management. A panel of international Experts, comprising hepatologists and oncologists, gathered to explore the challenges in effectively integrating immunotherapy in routine clinical practice. The aim of this review is to present the Experts' insights to inform treatment choice in HCC and BTC with a special emphasis on the role of currently available ICI-based therapies in shifting treatment paradigms and potentially reversing the natural course of these two deadly malignancies.

Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Address: Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Piazza delle Cliniche n 2, 90127 Palermo, Italy.; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, 20089 Rozzano, Milan, Italy. Electronic address: [email protected].; Department of Oncology - OncoHealth Institute, Fundación Jiménez Díaz University Hospital, Madrid, Spain; Department of Medical Oncology, The Christie NHS Foundation, Manchester, England, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK.; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy; Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.; Medical Oncology Unit, Ospedale del Mare, Napoli, Italy.; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.; Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, Vita-Salute San Raffaele University, Milan, Italy; Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.

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