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A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Systemic Drugs for Hepatocellular Carcinoma: What Do Recent Clinical Trials Reveal About Sequencing and the Emerging
Vera Himmelsbach1, Christine Koch1, Jörg Trojan1
1Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt, Germany.
Abstract:
Liver cancer was the fourth leading cause of cancer death in 2015 with increasing incidence between 1990 and 2015. Orthotopic liver transplantation, surgical resection and ablation comprise the only curative therapy options. However, due to the late manifestation of clinical symptoms, many patients present with intermediate or advanced disease, resulting in no curative treatment option being available. Whereas intermediate-stage hepatocellular carcinoma (HCC) is usually still addressable by transarterial chemoembolization (TACE), advanced-stage HCC is amenable only to pharmacological treatments. Conventional cytotoxic agents failed demonstrating relevant effect on survival also because their use was severely limited by the mostly underlying insufficient liver function. For a decade, tyrosine kinase inhibitor (TKI) sorafenib was the only systemic therapy that proved to have a clinically relevant effect in the treatment of advanced HCC. In recent years, the number of substances for systemic treatment of advanced HCC has increased enormously. In addition to tyrosine kinase inhibitors, immune checkpoint inhibitors (ICI) and antiangiogenic drugs are increasingly being applied. The combination of anti-programmed death ligand 1 (PD-L1) antibody atezolizumab and anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has become the new standard of care for advanced HCC due to its remarkable response rates. This requires more and more complex clinical decisions regarding tumor therapy. This review aims at summarizing recent developments in systemic therapy, considering data on first- and second-line treatment, use in the neoadjuvant and adjuvant setting and combination with locoregional procedures.
Insights
Systemic therapies for advanced liver cancer have evolved significantly. New treatments like immune checkpoint inhibitors and antiangiogenic drugs, including atezolizumab and bevacizumab, offer improved outcomes for hepatocellular carcinoma (HCC).
Area of Science:
- Hepatology and Oncology
- Pharmacological Therapies
- Cancer Treatment Modalities
Background:
- Liver cancer, particularly hepatocellular carcinoma (HCC), presents a significant global health challenge, being the fourth leading cause of cancer death in 2015.
- Many patients are diagnosed with intermediate or advanced disease, precluding curative options like transplantation, resection, or ablation.
- Traditional cytotoxic agents showed limited efficacy in advanced HCC due to poor liver function, with sorafenib being the sole effective tyrosine kinase inhibitor (TKI) for a decade.
Purpose of the Study:
- To review recent advancements in systemic therapy for advanced liver cancer.
- To summarize data on first- and second-line treatments, neoadjuvant/adjuvant settings, and combinations with locoregional procedures.
- To highlight the evolving landscape of hepatocellular carcinoma (HCC) treatment.
Main Methods:
- Literature review of recent developments in systemic therapy for advanced HCC.
- Analysis of clinical data on tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and antiangiogenic drugs.
- Evaluation of combination therapies, including atezolizumab and bevacizumab.
Main Results:
- The systemic treatment landscape for advanced HCC has expanded beyond TKIs to include ICIs and antiangiogenic agents.
- The combination of atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) has emerged as a new standard of care, demonstrating significant response rates.
- Complex clinical decisions are increasingly necessary for optimal tumor therapy management.
Conclusions:
- Systemic therapy for advanced HCC has made substantial progress, offering new hope for patients.
- The combination of atezolizumab and bevacizumab represents a major breakthrough, improving outcomes in advanced HCC.
- This review provides a comprehensive overview to guide complex therapeutic choices in HCC management.
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