Systemic Therapy for Advanced Hepatocellular Carcinoma

Publication Date: March 18, 2024
Last Updated: March 19, 2024

Key Points

Key Points

  • This guideline update adds the first-lizumab + bevacizumab (atezo-bev).
  • Various treatment options are recommended for patients who have contraindications to these first-line therapy combinations, and for later-line treatment.

Treatment

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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Figure 1. Systemic Therapy for Advanced Hepatocellular Carcinoma Algorithm

1 The target population includes patients who are no longer candidates for surgical or liver-directed therapies, i.e. patients with characteristics such as multifocal and/or infiltrative disease within the liver, vascular invasion or extrahepatic spread.

2 Treatment options should be discussed within a multidisciplinary team.

3 Patients in the IMbrave150 trial of atezo+bevwere required to have undergone esophagogastroduodenoscopy (EGD) within 6 months of trial initiation and to have received treatment for esophageal varices when necessary.

4 Considerations include underlying liver function, bleeding risk, presence of portal hypertension, extent of extrahepatic spread, tumor burden, and major vascular invasion.

5 While there is currently no published evidence to support a recommendation for durva+treme, the ASCO Advanced HCC Expert Panel agreed that this option may be considered following first-line treatment with atezo+bev.

6 There is no data available to select patients for atezo+bev vs. second-line therapy with a TKI.

7 Pembrolizumab or nivolumab are reasonable options that may be considered for appropriate candidates following first-line therapy with sorafenib or lenvatinib.

Recommendation Grading

Abbreviations

  • AFP: Alphafetoprotein
  • ASCO: American Society Of Clinical Oncology
  • ECOG: Eastern Cooperative Oncology Group
  • EGD: Esophagogastroduodenoscopy
  • HBV: Hepatitis B Virus
  • HCC: Hepatocellular Carcinoma
  • HCV: Hepatitis C Virus
  • RCT: Randomized Controlled Trial
  • TKI: Tyrosine Kinase Inhibitor
  • atezo + bev: Atezolizumab + Bevacizumab

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

Disclaimer

This pocket guide is derived from recommendations in the American Society of Clinical Oncology Guideline. This resource is a practice tool based on ASCO® practice guidelines and is not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients. This pocket guide does not purport to suggest any particular course of medical treatment. Use of the practice guidelines and this resource are voluntary. The practice guidelines and additional information are available at www.asco.org/gastrointestinal-cancer-guidelines. Copyright © 2024 by American Society of Clinical Oncology. All rights reserved.