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Updated: Oct 23, 2025
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Immunotherapy in Hepatocellular Carcinoma
Claudia A M Fulgenzi1, Thomas Talbot2, Sam M Murray3
1Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy.
Opinion Statement:
Patients with hepatocellular carcinoma (HCC) have been traditionally deprived from highly effective systemic therapy options in the past decades. The multi-targeted tyrosine kinase inhibitor sorafenib, approved in 2008, remained the only treatment option for advanced HCC for over a decade. A number of molecularly targeted therapies such as lenvatinib, regorafenib, cabozantinib, and ramucirumab have significantly widened treatment options in patients with advanced HCC. However, emergence of resistance and long-term toxicity from treatment are barriers to long-term survivorship. Immunotherapy is at the focus of intense research efforts in HCC. Whilst targeting of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte 4 (CTLA-4) is associated with radiologically measurable disease-modulating effects in HCC, monotherapies fell short of demonstrating evidence of significant survival extension in advanced disease. Atezolizumab and bevacizumab were the first immunotherapy regimen to demonstrate clear superiority in improving the survival of patients with unresectable HCC compared to sorafenib, paving the way for immunotherapy combinations. As the treatment landscape of HCC rapidly evolves, with immunotherapy integrating within early- and intermediate-stage disease treatment algorithms, lack of level 1 evidence on sequencing of therapeutic strategies and lack of head-to-head comparisons across immunotherapy combinations will affect prescribing of immunotherapy in routine practice. In the absence of predictive biomarkers, choice of immunotherapy over kinase inhibitors will continue to remain an empirical exercise, guided by balancing anti-tumour efficacy with toxicity considerations in the individual patient.
Insights
Hepatocellular carcinoma (HCC) treatment has evolved beyond sorafenib with new targeted therapies and immunotherapies. While immunotherapy combinations show promise, optimal sequencing and biomarker use are crucial for advanced HCC survivorship.
Area of Science:
- Hepatology
- Medical Oncology
- Immunotherapy
Background:
- Hepatocellular carcinoma (HCC) treatment options were limited for decades, with sorafenib being the sole systemic therapy for advanced stages for over ten years.
- Recent advancements introduced molecularly targeted therapies (e.g., lenvatinib, regorafenib) and immunotherapies, expanding treatment choices for advanced HCC.
- Despite progress, treatment resistance and long-term toxicity remain significant challenges impacting patient survivorship.
Purpose of the Study:
- To review the evolving treatment landscape for advanced hepatocellular carcinoma (HCC).
- To discuss the role and limitations of targeted therapies and immunotherapies in HCC management.
- To highlight the need for evidence-based strategies regarding immunotherapy sequencing and biomarker development.
Main Methods:
- Review of recent clinical trial data and treatment guidelines for advanced HCC.
- Analysis of the efficacy and toxicity profiles of targeted therapies and immunotherapies.
- Discussion of current challenges and future directions in HCC systemic therapy.
Main Results:
- Sorafenib was the standard of care for advanced HCC until recently; newer targeted agents have emerged.
- Immunotherapy monotherapies showed limited survival benefits, but combinations like atezolizumab and bevacizumab improved survival compared to sorafenib.
- The integration of immunotherapy into earlier stages of HCC treatment is ongoing, but evidence on optimal sequencing and head-to-head comparisons is lacking.
Conclusions:
- The treatment of advanced HCC is rapidly evolving with the advent of targeted therapies and immunotherapies.
- Immunotherapy combinations represent a significant advancement, but challenges remain regarding treatment sequencing, predictive biomarkers, and managing toxicity.
- Personalized treatment decisions in HCC require balancing anti-tumor efficacy with individual patient toxicity considerations.
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