Related Experiment Video
Updated: Aug 17, 2026
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Systemic Treatment Options in Hepatocellular Carcinoma
Lorenza Rimassa1, Tiziana Pressiani1, Philippe Merle2
1Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center - IRCCS, Milan, Italy.
Background:
Patients with advanced hepatocellular carcinoma (HCC) typically have poor survival outcomes. Until recently, sorafenib was the only systemic therapy option available and no agents were approved after sorafenib failure. However, rapid changes are beginning to emerge in the treatment landscape of advanced HCC, with approvals of regorafenib, nivolu-mab, lenvatinib, pembrolizumab, and cabozantinib and positive phase II/III clinical trial results with other agents.
Summary:
Here, we provide a comprehensive overview of the clinical trial data of systemic agents that are currently approved for advanced HCC (sorafenib, regorafenib, and nivolumab), including agents recently approved in 2018 (lenvatinib, pembrolizumab, and cabozantinib) and those with recent positive phase II/III results (ramucirumab). Key features of the clinical trial design, including patient selection criteria, the use of biomarkers in HCC, and criteria for efficacy assessment, and their implications in real-world practice are discussed. Important ongoing and planned trials in advanced HCC are summarized to provide a glimpse into the future of advanced HCC treatment. From a physician's viewpoint, the treatment algorithms for advanced HCC are undergoing significant changes, as additional and imminent approvals impact the choices of first- and second-line treatment and decisions regarding the timing of therapy initiation. With these additional choices at hand, treatment sequencing remains a complex task and should take patient selection and tolerance profiles into account.
Key Messages:
The treatment of advanced HCC remains challenging and complex. The rapid developments in systemic therapy for advanced HCC should be considered when determining the best choice and sequence of treatment for patients with advanced HCC.
Insights
Systemic therapies for advanced hepatocellular carcinoma (HCC) are rapidly evolving. New agents and treatment sequences offer improved options, but careful patient selection and tolerance assessment are crucial for effective advanced HCC management.
Area of Science:
- Hepatocellular Carcinoma Research
- Oncology Drug Development
- Clinical Trial Analysis
Background:
- Advanced hepatocellular carcinoma (HCC) historically had limited treatment options with poor survival.
- Sorafenib was the sole approved systemic therapy, with no agents available post-progression.
- Recent years have seen significant advancements with multiple new drug approvals and positive trial outcomes.
Purpose of the Study:
- To provide a comprehensive overview of systemic agents approved for advanced HCC.
- To discuss clinical trial design, biomarker use, and efficacy assessment in HCC.
- To summarize ongoing and future clinical trials in advanced HCC treatment.
Main Methods:
- Review of clinical trial data for approved systemic agents (sorafenib, regorafenib, nivolumab, lenvatinib, pembrolizumab, cabozantinib).
- Analysis of recent positive phase II/III trial results (e.g., ramucirumab).
- Discussion of implications of trial design features for real-world practice.
Main Results:
- Multiple systemic agents are now approved for advanced HCC, expanding treatment options beyond sorafenib.
- Recent approvals in 2018 include lenvatinib, pembrolizumab, and cabozantinib.
- Ongoing trials and emerging data suggest a dynamic future treatment landscape.
Conclusions:
- The treatment landscape for advanced HCC is rapidly changing with new therapeutic options.
- Treatment sequencing is complex and requires consideration of patient selection and tolerance.
- Effective management of advanced HCC necessitates awareness of evolving systemic therapies.
Related Concept Videos
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Tumor Immunotherapy
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...