Success is not final, failure is not fatal: The changing landscape of systemic therapy for advanced hepatocellular carcinoma

Abstract

Objective: To review the history of development of systemic therapy for advanced hepatocellular carcinoma (HCC). Data Sources: Published clinical trials of single-agent targeted agents, single-agent immune checkpoint inhibitors (ICI), and ICI-based combination regimens. Results: Key lessons learned from previous positive and negative clinical trials included design of more efficient clinical trials and incorporation of trial endpoints most relevant to clinical benefit. Major challenges included prioritization of novel combination therapies for clinical trials and development of predictive biomarkers. Conclusion: The improved efficacy and safety of systemic therapy will impact on future multi-disciplinary management of HCC through more extensive integration with liver-directed therapy for different stages of HCC patients.