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.
618

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.
618

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.
618

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.
618

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

Publication Month/Year

March 18, 2024

Last Updated Month/Year

April 9, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

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

Data Supplement, Evidence Tables

Methodology

Number of Source Documents
122
Literature Search Start Date
May 15, 2020
Literature Search End Date
October 5, 2023