Promising PD-1 antagonists for liver cancer: an evaluation of phase II and III results

Expert Opin Emerg Drugs. 2024 Dec;29(4):369-382. doi: 10.1080/14728214.2024.2430493. Epub 2024 Dec 5.

Abstract

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

Areas covered: This review explores immune checkpoint inhibitors (ICIs), specifically PD-1, PD-L1, and CTLA-4 inhibitors, as emerging treatments for advanced HCC. It discusses data from phase II and III trials evaluating ICI combinations with tyrosine kinase inhibitors (TKIs), anti-angiogenic agents, and locoregional treatments like Transarterial Chemoembolization (TACE). Clinical outcomes, including progression-free survival and response rates, were analyzed alongside the incidence and management of immune-related adverse events (irAEs). A systematic review approach ensured comprehensive, high-quality study inclusion.

Expert opinion: ICI-based therapies and their combinations are transforming advanced HCC treatment, offering improved outcomes and potential survival benefits. However, these therapies need optimization in sequencing and selection, particularly considering variations in liver function and disease stage. Effective management of adverse effects is critical to maximize clinical benefits. Further research is required to develop personalized strategies, tailoring treatments to patient-specific factors and enhancing safety and effectiveness in HCC management.

Keywords: Immunotherapy; clinical trials; combination therapy; hepatocellular carcinoma; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • B7-H1 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / antagonists & inhibitors
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Clinical Trials, Phase II as Topic
  • Humans
  • Immune Checkpoint Inhibitors* / administration & dosage
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / pharmacology
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Neoplasm Staging
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Progression-Free Survival
  • Survival Rate

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human
  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen