Systemic therapy for HCC: Doublets, triplets and beyond.

Immune checkpoint inhibitor-based combinations are now the standard first-line systemic therapy for advanced hepatocellular carcinoma, showing improved survival and response rates.

• Why it matters: HCC is a leading cause of cancer-related death worldwide, and effective systemic treatments are crucial due to its biological heterogeneity and limited predictive biomarkers, which hinder personalized therapy.
• What they did: The review summarizes current systemic therapies, including ICI-based combinations, and discusses emerging strategies such as bispecific antibodies, cellular therapies, vaccines, oncolytic viruses, and novel targeted agents, along with biomarker approaches.
• The result: While ICI combinations improve outcomes, triplet immunotherapy has not shown clear benefit and increases toxicity; ongoing research aims to enable more precise, effective treatment selection.