The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?
Ther Adv Med Oncol. 2023 Jan 10;15:17588359221148029.doi: 10.1177/17588359221148029. eCollection 2023.
1Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy.
2Drug Development Unit, Sarah Cannon Research Institute UK, London, UK.
3Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
4Division of Internal Medicine, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
5Department of Surgery & Cancer, Imperial College London, London, UK.
6Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
7Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele (Milan), Italy.
8Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano (Milan), Italy.
Abstract
The treatment landscape of advanced hepatocellular carcinoma (HCC) has broadened with immune checkpoint inhibitors (ICIs) setting a novel standard of care. With the increased number of therapies either in first or in further line, disentangling the possible treatment sequences has become much more complex. Yet, all the second-line therapies have been evaluated after sorafenib. After ICIs, offering multikinase inhibitors is a widespread approach, either shifting forward sorafenib or lenvatinib, or choosing among regorafenib or cabozantinib, already approved in the refractory setting. Under specific circumstances, ICIs could be maintained beyond disease progression in patients with proven clinical benefit, as supported by some data emerging from phase III clinical trials with immunotherapy in HCC. Rechallenge with ICIs is an additional attractive alternative, although requiring careful and individual evaluation as efficacy and safety of such a strategy have not been yet clarified. Still, a considerable number of patients displays primary resistance to ICIs and might benefit from antiangiogenics either alone or in addition to ICIs instead. Hopefully, the ongoing clinical trials will enlighten regarding the most effective treatment pathways. The identification of predictive correlates of response to immunotherapy will help treatment allocation at each stage, thus representing an urgent matter to address in HCC research. With programmed death ligand 1 expression, tumor mutational burden, and microsatellite status being inadequate biomarkers in HCC, patient characteristics, drug safety profile, and regulatory approval remain key elements to acknowledge in routine practice. Despite the tissue remaining a preferred source, biomarkers discovery could take advantage of liquid biopsy to overcome the matter of tissue availability and track tumor changes. Lastly, tumor genetic phenotypes, tumor microenvironment features, gut microbiome, and markers of immune response and systemic inflammation are all potential emergent predictors of response to ICIs, pending validation in the clinical setting.