Systemic Therapy for Hepatocellular Carcinoma

Publication Date: February 21, 2022

First-line treatment for HCC in patients with preserved liver function

In patients with HCC with preserved liver function not eligible for LRT or resection or with metastatic disease, the AGA suggests atezolizumab+bevacizumab over sorafenib. ( Low , Conditional (weak) )
Comment: Gastrointestinal bleeding is a known adverse effect of bevacizumab and individuals should undergo endoscopic evaluation and treatment for esophageal varices before treatment.
612
In patients with HCC with preserved liver function not eligible for LRT or resection or with metastatic disease who are not candidates for treatment with atezolizumab+bevacizumab, the AGA suggests either lenvatinib or sorafenib over no systemic therapy. ( Low , Conditional (weak) )
Comments: Patients who place a higher value on delayed radiologic disease progression and lower value on the increase in adverse events (both serious and leading to discontinuation of the drug) may reasonably choose lenvatinib over sorafenib. Patients who place a higher value on blood pressure control and a lower value on the adverse skin reactions would reasonably select sorafenib over lenvatinib. It should be noted that lenvatinib has not been studied in patients with invasion of the main portal vein and thus may not be appropriate for this population. Patients who place a higher value on the adverse events associated with sorafenib or lenvatinib and lower value on the reduction in mortality (2.8 mo for sorafenib, unknown for lenvatinib) may reasonably select no systemic therapy.
612

Second-line treatment for individuals with disease progression or intolerance to first-line systemic therapy

In patients with HCC with preserved liver function not eligible for LRT or resection or with metastatic disease, who had progression of disease on sorafenib, the AGA suggests cabozantinib over no systemic therapy. ( Very Low , Conditional (weak) )
Comment: Patients who place a higher value on adverse effects associated with cabozantinib and lower value on the reduction in mortality (2.2 mo) may reasonably decline cabozantinib.
612
In patients with HCC with preserved liver function not eligible for LRT or resection or with metastatic disease, and who had progression of disease on sorafenib, the AGA suggests using pembrolizumab over no systemic therapy. ( Low , Conditional (weak) )
Comments: Patients who place a higher value on adverse effects associated with pembrolizumab and lower value on the reduction in mortality (3.3 mo) may reasonably decline pembrolizumab. Patients with main portal vein invasion or inferior vena cava or cardiac involvement of HCC on the basis of imaging were not studied.
612
In patients with HCC with preserved liver function and AFP >400 ng/mL not eligible for LRT or resection or with metastatic disease who had progression of disease on sorafenib, the AGA suggests using ramucirumab over no systemic therapy. ( Low , Conditional (weak) )
Comments: Patients who place a higher value on adverse effects associated with ramucirumab and lower value on the reduction in mortality (1.2 mo) may reasonably decline ramucirumab. In patients with AFP < 400 ng/mL, the AGA suggests against the use of ramucirumab.
612
In patients with HCC with preserved liver function not eligible for LRT or resection or with metastatic disease, who had progression of disease on sorafenib, the AGA suggests regorafenib over no systemic therapy. ( Low , Conditional (weak) )
Comment: Patients who place a higher value on adverse effects associated with regorafenib and lower value on the reduction in mortality (2.8 mo) may reasonably decline regorafenib. Regorafenib should not be used in patients who did not tolerate sorafenib due to toxicity.
612

Systemic therapy for HCC in patients with poor liver function

In patients with HCC with poor liver function not eligible for LRT or resection or with metastatic disease, the AGA suggests against routine use of sorafenib. ( Very Low , Conditional (weak) )
Comment: Patients, particularly those who are not CTP C, who place a higher value on the uncertain reduction in mortality and lower value on the harms, may reasonably select to use sorafenib.
612

Systemic therapy for HCC as adjuvant therapy

In patients with HCC undergoing curative surgical resection, the AGA suggests against adjuvant sorafenib therapy. ( Low , Conditional (weak) )
612
In patients with HCC undergoing curative local ablation, the AGA suggests against adjuvant sorafenib therapy. ( Low , Conditional (weak) )
612
In patients with HCC undergoing TACE LRT, the AGA suggests against adjuvant sorafenib therapy. ( Very Low , Conditional (weak) )
612
In patients with HCC undergoing TACE LRT the AGA suggests against adjuvant bevacizumab therapy. ( Very Low , Conditional (weak) )
612

Recommendation Grading

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Overview

Title

Systemic Therapy for Hepatocellular Carcinoma

Authoring Organization

Publication Month/Year

February 21, 2022

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Document Objectives

Hepatocellular carcinoma (HCC), the most common primary liver cancer, remains a deadly cancer, with an incidence that has tripled in the United States since 1980. In recent years, new systemic therapies for HCC have been approved and a critical assessment of the existing data is necessary to balance benefits and harms and inform the development of evidence-based guidelines.

Inclusion Criteria

Male, Female, Adult, Infant

Health Care Settings

Ambulatory, Outpatient, Operating and recovery room

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D006528 - Carcinoma, Hepatocellular

Keywords

systemic therapy, hepatocellular carcinoma, liver cancer, hcc

Source Citation

Grace L. Su, Osama Altayar, Robert O’Shea, Raj Shah, Bassam Estfan, Candice Wenzell, Shahnaz Sultan, Yngve Falck-Ytter, AGA Clinical Practice Guideline on Systemic Therapy for Hepatocellular Carcinoma, Gastroenterology, Volume 162, Issue 3, 2022, Pages 920-934, ISSN 0016-5085, https://doi.org/10.1053/j.gastro.2021.12.276.

Supplemental Methodology Resources

Data Supplement, Technical Review

Methodology

Number of Source Documents
132
Literature Search Start Date
January 1, 2007
Literature Search End Date
May 15, 2020