What is the recommended immunotherapy regimen, including doses, for the treatment of hepatocellular carcinoma (HCC)?

Recommended Immunotherapy Regimens for Hepatocellular Carcinoma (HCC)

For patients with unresectable hepatocellular carcinoma, the recommended first-line immunotherapy regimens are atezolizumab plus bevacizumab (1200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) or tremelimumab plus durvalumab (single dose of tremelimumab 300 mg with durvalumab), both of which have demonstrated superior survival outcomes compared to sorafenib. 1, 2

First-Line Immunotherapy Options

Atezolizumab plus Bevacizumab

• Dosing: 1200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks 3
• Efficacy: Demonstrated superior overall survival (19.2 months vs 13.4 months) compared to sorafenib 3
• Key considerations:
  • Requires endoscopic screening for esophageal varices prior to treatment 2
  • Contraindicated in patients with grade 2 or higher esophageal varices due to bleeding risk 2
  • Contraindicated in patients with main portal vein invasion or clear bile duct invasion 2

Tremelimumab plus Durvalumab

• Dosing: Single dose of tremelimumab 300 mg with durvalumab 1
• Efficacy: Demonstrated significant improvement in overall survival compared to sorafenib in the HIMALAYA trial 1
• Key considerations:
  • Lower risk of hemorrhage compared to bevacizumab-containing regimens 2
  • Does not require endoscopy as a prerequisite 2
  • May be preferred in patients with esophageal varices or bleeding risk 2

Patient Selection Criteria for First-Line Therapy

• Child-Pugh A liver function (well-preserved liver function) 1, 2
• ECOG Performance Status 0-1 2
• No prior systemic therapy 1

Second-Line Immunotherapy Options

For patients who progress on or are intolerant to first-line therapy:

Pembrolizumab Monotherapy

• Has accelerated FDA approval as a second-line option 1
• Objective response rate of 17% in patients who progressed on sorafenib 2

Nivolumab plus Ipilimumab

• Has accelerated FDA approval as a second-line option 1
• Objective response rate of 33% in patients who progressed on sorafenib 2

Monitoring and Response Assessment

• Tumor response should be assessed using dynamic CT or MRI studies every 3 months 2
• Modified RECIST (mRECIST) criteria should be used to evaluate response to therapy 2
• Monitor for immune-related adverse events, which can occasionally be life-threatening 2

Potential Adverse Events

Atezolizumab plus Bevacizumab

• Most common adverse reactions: hypertension (29.8%), fatigue (20.4%), and proteinuria (20.1%) 1

Tremelimumab plus Durvalumab

• Anti-tremelimumab antibodies detected in 11% of patients 1
• Anti-durvalumab antibodies detected in 3.1% of patients 1

Emerging Concepts

• Combination strategies with local therapies (TACE, radiation) are under investigation 2
• Conversion therapy (using systemic therapy to downstage initially unresectable disease) is showing promise 4
• In a proof-of-concept study, 35% of patients with intermediate-stage HCC achieved complete response with atezolizumab plus bevacizumab followed by curative conversion therapy 4

Treatment Algorithm

1. First-line therapy (for unresectable HCC, Child-Pugh A):

   • For patients without esophageal varices or after successful management of varices: Atezolizumab plus bevacizumab
   • For patients with esophageal varices or bleeding risk: Tremelimumab plus durvalumab
   • For patients with contraindications to immunotherapy: Consider lenvatinib or sorafenib 1, 2

2. Second-line therapy (after progression on first-line):

   • Pembrolizumab monotherapy or nivolumab plus ipilimumab 1, 2

By following this evidence-based approach to immunotherapy for HCC, clinicians can optimize treatment outcomes while managing potential adverse events for patients with this challenging malignancy.