Author information

¹Digestive Disease Center (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

²IRCCS, San Raffaele, Roma, Italy.

³Department of Liver Cancer and Innovative Therapy Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Clichy, France.

⁴Departement de Pharmacie, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Clichy, France.

⁵Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, Rome, Italy.

⁶Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), INSERM, Paris, France.

Abstract

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a significant cause of cancer-related morbidity and mortality. Limited treatment options for advanced stages emphasize the need for effective therapies.

Areas covered: This review examines immune checkpoint inhibitors (ICIs), specifically PD-1, PD-L1, and CTLA-4 inhibitors, as novel treatments for advanced HCC. The review includes data from phase II and III clinical trials that evaluate ICI combinations with tyrosine kinase inhibitors (TKIs) and anti-angiogenic agents, as well as locoregional treatments such as Transarterial Chemoembolization (TACE). Clinical outcomes, including progression-free survival and overall response rates, were analyzed along with the incidence and management of immune-related adverse events (irAEs). A systematic literature review method was applied to ensure the inclusion of comprehensive, high-quality studies.

Expert opinion: ICI-based therapies and their combinations are reshaping the treatment landscape for advanced HCC by providing improved outcomes and potentially extending patient survival. Although promising, these therapies require further refinement to optimize sequencing and treatment selection, especially for patients with different levels of liver function and disease stages. Managing adverse effects effectively is essential for maximizing the benefits of these therapies in clinical practice. Continued research is needed to support the development of personalized approaches that can better tailor these treatments to individual patient needs, ultimately enhancing the overall effectiveness and safety of HCC management.