Journal: Journal of gastroenterology and hepatology
This review article outlines current and emerging systemic and locoregional treatment strategies for advanced hepatocellular carcinoma (HCC).
Key points:
- Epidemiology and unmet need: HCC is the predominant primary liver cancer, with most patients presenting at advanced stages where curative options are not feasible.
- Current first-line standard: Over the past five years, combination immunotherapy has replaced tyrosine kinase inhibitors (TKIs) as standard first-line treatment. Regimens pair an anti–PD-(L)1 agent with either an anti–CTLA-4 antibody or an anti-VEGF agent, delivering higher response rates and survival than TKIs.
- Limitations of current immunotherapy: Only about 20–30% of patients respond to first-line immunotherapy combinations, and roughly half of responders progress by 6 months, underscoring a substantial need for more effective strategies.
- Post-immunotherapy options: For patients progressing on immunotherapy, recent prospective studies support the continued role of multiple TKIs, with evidence for both efficacy and safety in this setting.
- Novel systemic approaches: Strategies under investigation include triplet immunotherapy regimens, such as adding a third immune checkpoint inhibitor to existing combinations to deepen and prolong responses.
- Locoregional–systemic combinations: There is growing interest in integrating locoregional therapy with systemic treatment in advanced disease. Three phase 3 trials—EMERALD-1, LEAP-012, and TALENTACE—have shown survival benefit when transarterial chemoembolization (TACE) is combined with immunotherapy versus TACE alone. These combinations yield higher response rates and enable downstaging or conversion to potentially curative therapies in selected patients.
- Cellular therapies: Early-phase data on cellular therapies indicate promise and suggest immunotherapy in HCC may extend beyond checkpoint inhibitors, although this remains investigational.
Overall, the review synthesizes an evolving landscape in advanced HCC, emphasizing the shift toward combination immunotherapy, the role of TKIs after immunotherapy failure, and the emerging potential of TACE–immunotherapy combinations and cellular therapies to further improve outcomes.