Systemic Therapy for Advanced Hepatocellular Carcinoma
Publication Date: March 18, 2024
Last Updated: March 19, 2024
Treatment
First-line Therapy
Recommendation 1.1
Atezo+bev or durva+treme may be offered as first-line treatment for patients with Child-Pugh class A, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1 advanced HCC. (, , H , S )
Qualifying statements:
- For patients receiving atezo+bev, screening for and management of esophageal varices when present are recommended prior to initiation of therapy and according to institutional guidelines.
- The choice between treatment options in Recommendation 1.1 should be made through a discussion involving the physician and patient (and caregiver, where applicable), and should include factors such as medical history, toxicities associated with treatment, cost, goals of treatment, patient preference, and expected treatment benefit.
- When choosing between the two combination therapy options, consider risk of bleeding and thrombosis with the vascular endothelial growth factor (VEGF) inhibitor bevacizumab.
- Patients with active or previously documented autoimmune disease should consider the risk of immune-related adverse effects associated with atezo and durva+treme.
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Recommendation 1.2
Where there are contraindications to atezo+bev or durva+treme, sorafenib, lenvatinib, or durvalumab may be offered as first-line treatment for patients with Child-Pugh class A, and ECOG PS 0–1 advanced HCC. (, , I , S )
Qualifying statement:
- The choice between treatment options should take into account the factors listed in the second qualifying statement to Recommendation 1.1.
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Second-line Therapy
Recommendation 2.1
Following first-line treatment with atezo+bev, second-line therapy with a tyrosine kinase inhibitor (TKI) (i.e., sorafenib, lenvatinib, or cabozantinib), or ramucirumab (alpha-fetoprotein [AFP] ≥400 ng/mL) are recommended. (, , L , W )
Qualifying statements:
- The Expert Panel also agreed that nivolumab + ipilimumab (nivo+ipi) is an option that may be considered following first-line treatment with atezo+bev, although the evidence for nivo+ipi is limited to data from case series.
- While there is currently no published evidence to support a recommendation for durva+treme, the Expert Panel agreed that this option may be considered following first-line treatment with atezo+bev.
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Recommendation 2.2
Following first-line treatment with durva+treme, second-line therapy with a TKI is recommended. (, , L , W )
Qualifying statement:
- The Expert Panel also agreed that atezo+bev may be considered following durva+treme for patients who do not have contraindications to the former combination, although there is no data available to select patients for this combination therapy vs. second-line therapy with a TKI.
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Recommendation 2.3
Following first-line treatment with sorafenib or lenvatinib, second-line therapy with another TKI (cabozantinib or regorafenib), ramucirumab (AFP ≥400 ng/mL), nivo+ipi, or durvalumab may be recommended for appropriate candidates. Atezo+bev or durva+treme may be considered for patients who may not have had access to these therapies in the first-line setting, and do not have contraindications to these combinations. Considerations regarding choice of therapy are included in the full ASCO guideline. (, , I , W )
Qualifying statement:
- In addition, pembrolizumab or nivolumab are reasonable options that may be considered for appropriate candidates following first-line therapy with sorafenib or lenvatinib.
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Third-line Therapy
Recommendation 3.1
Third-line therapy may be considered in Child-Pugh A patients with good performance status, using one of the agents listed previously that has a non-identical mechanism of action with previously received therapy. (, , L , W )
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Child-Pugh class B
Recommendation 4.1
The Expert Panel agrees on a cautious approach to systemic therapy in advanced HCC patients who are Child-Pugh class B with good PS, considering underlying liver function, bleeding risk, presence of portal hypertension, extent of extrahepatic spread, tumor burden, and major vascular invasion. Limited data suggest that regimens typically used for Child-Pugh A can be beneficial in untreated patients with Child-Pugh B cirrhosis. Given the modest expectations for clinical benefit from systemic therapy in this population, the Expert Panel emphasizes shared decision-making with patients. (, , L , W )
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Recommendation Grading
Overview
Title
Systemic Therapy for Advanced Hepatocellular Carcinoma
Authoring Organization
American Society of Clinical Oncology
Publication Month/Year
March 18, 2024
Last Updated Month/Year
November 7, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC).
Target Patient Population
Patients with advanced hepatocellular carcinoma.
PICO Questions
What are the preferred treatment options for first-line systemic therapy for patients with advanced hepatocellular carcinoma?
What are the preferred treatment options for second- or later-line therapy for patients with advanced hepatocellular carcinoma?
Inclusion Criteria
Male, Female, Adult, Older adult
Health Care Settings
Ambulatory, Emergency care, Home health, Hospice, Hospital, Long term care
Intended Users
Nurse, nurse practitioner, physician, physician assistant, social worker
Scope
Treatment, Management
Diseases/Conditions (MeSH)
D006528 - Carcinoma, Hepatocellular
Keywords
hepatocellular carcinoma, child-pugh class A liver disease, liver diseases
Source Citation
John D. Gordan, MD, PhD; Erin B. Kennedy, MHSc; Ghassan K. Abou-Alfa, MD, MBA, et al. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline. J Clin Oncol. 2024 March 19. doi: JCO.23.02745
Supplemental Methodology Resources
Methodology
Number of Source Documents
122
Literature Search Start Date
May 15, 2020
Literature Search End Date
October 5, 2023