Efficacy and Adverse Events of Sorafenib in Advanced Hepatocellular Carcinoma

Sorafenib, a multikinase inhibitor targeting RAF kinases and vascular endothelial growth factor receptors, remains the first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Clinical trials and real-world studies have consistently shown a modest extension of overall survival by approximately three to five months, as well as a delay in radiological progression. Efficacy varies according to tumour burden, liver function and performance status. Common adverse events include hand-foot skin reaction, diarrhoea, fatigue and hypertension, often necessitating dose reductions or temporary discontinuation. Liver function deterioration and early disease progression predict poorer outcomes. Despite these limitations, sorafenib has established a global benchmark for systemic therapy in HCC, informing the design of subsequent agents and combination regimens.

Research from Nature Portfolio

Recent work has introduced a patient-centric three-dimensional spheroid model that faithfully recapitulates key aspects of hepatocellular carcinoma biology, including the Barcelona Clinic Liver Cancer molecular subclasses and epigenetic alterations. By applying a target-independent cell killing (TICK) exclusion strategy, investigators were able to quantify therapeutic response to sorafenib, cabozantinib and lenvatinib in a blinded fashion. In a series of 37 case studies, this approach correctly predicted clinical outcomes to sorafenib in 34 instances, demonstrating its potential to personalise treatment choices and accelerate drug discovery. This model offers a robust preclinical platform for dissecting mechanisms of resistance and for exploring combination strategies in a patient-specific context.

Efficacy and Adverse Events of Sorafenib in Advanced Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in efficacy and adverse events of sorafenib in advanced hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

BCLC staging: A classification system for HCC that combines tumour burden, liver function and patient performance status.

ECOG performance status: A scale (0–5) assessing a patient’s level of functioning and ability to tolerate treatment.

Overall survival (OS): The interval from treatment initiation to death from any cause.

Time to progression (TTP): The duration from therapy start to radiologically confirmed tumour progression.

Patient-derived spheroid model: A three-dimensional culture system that mimics the architectural and molecular features of a patient’s tumour.

Target-independent cell killing (TICK): An assay strategy that evaluates therapeutic response without relying on direct target engagement.

References

1. Prognostic Impact of Metastatic Site in Patients Receiving First-Line Sorafenib Therapy for Advanced Hepatocellular Carcinoma. Cancers (2023).
2. Modelling hepatocellular carcinoma microenvironment phenotype to evaluate drug efficacy. Scientific Reports (2025).
3. Real-World, Observational, Retrospective Study to Evaluate the Effectiveness and Safety of Treatment with Sorafenib in Patients with Advanced Hepatocellular Carcinoma. Current Oncology (2024).
4. Systemic treatments for hepatocellular carcinoma: challenges and future perspectives. Hepatic Oncology (2018).
5. Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib. Liver International (2019).