What are the treatment options for advanced Hepatocellular Carcinoma (HCC) in patients who are not eligible for Lenvatinib (lenvatinib)?

Treatment Options for HCC Patients Not Eligible for Lenvatinib

For patients with advanced hepatocellular carcinoma (HCC) who are not eligible for lenvatinib, the recommended first-line treatment is atezolizumab plus bevacizumab, followed by sorafenib, regorafenib, cabozantinib, or ramucirumab as subsequent options based on specific patient characteristics. 1

First-Line Treatment Options

Atezolizumab Plus Bevacizumab

• First choice for patients with:
  • Preserved liver function (Child-Pugh A)
  • Good performance status (ECOG 0-1)
  • No contraindications to bevacizumab
• Requires endoscopic evaluation and treatment of esophageal varices before starting treatment due to bleeding risk 1
• Superior to sorafenib in overall survival and progression-free survival 1

Sorafenib

• Alternative first-line option for patients who:
  • Cannot receive atezolizumab plus bevacizumab
  • Have Child-Pugh A or selected Child-Pugh B liver function
  • Have ECOG PS 0-2 1
• Standard dose: 800 mg daily 1
• Median overall survival: 10.7 months vs 7.9 months with placebo 1
• Common adverse events: hand-foot skin reaction (54%), diarrhea, fatigue 2

Second-Line Treatment Options

Regorafenib

• Standard of care for patients who:
  • Have tolerated sorafenib but progressed on it
  • Have well-preserved liver function (Child-Pugh A)
  • Have good performance status (ECOG PS 0-1) 1
• Not specifically studied after lenvatinib failure 3

Cabozantinib

• Indicated for patients who:
  • Have been previously treated with sorafenib 4
  • Have progressive disease on one or two systemic therapies
  • Have well-preserved liver function and ECOG PS 0-1 1
• Targets VEGFR2, MET, and AXL receptor tyrosine kinases 1
• Objective response rate: 4% 5

Ramucirumab

• Specifically for patients with:
  • Baseline AFP ≥400 ng/mL
  • Well-preserved liver function
  • ECOG PS 0-1 1
• Can be considered after sorafenib failure 1

Immunotherapy Options

• Nivolumab can be considered in patients who:
  • Are intolerant to or have progressed on tyrosine kinase inhibitors
  • Have well-preserved liver function 1
• Pembrolizumab and ipilimumab plus nivolumab are also approved after sorafenib treatment 3

Locoregional Treatment Options

For selected patients with advanced HCC without extrahepatic spread:

• TACE (Transarterial Chemoembolization):

  • Can be considered for patients with advanced, non-metastatic HCC with macrovascular invasion 1
  • Option for patients with intermediate-stage HCC 1

• SIRT (Selective Internal Radiotherapy):

  • Alternative for patients with advanced HCC without extrahepatic disease 1
  • Similar survival outcomes but better quality of life compared to sorafenib in patients with locally advanced HCC with major vascular involvement 1

• HAIC (Hepatic Arterial Infusion Chemotherapy):

  • Option for selected patients with advanced HCC 1
  • May be used alone or in combination with sorafenib 1

Treatment Selection Algorithm

1. Assess patient eligibility for atezolizumab plus bevacizumab:

   • If eligible → Recommend atezolizumab plus bevacizumab
   • If not eligible → Proceed to step 2

2. Assess patient eligibility for sorafenib:

   • If eligible → Recommend sorafenib
   • If not eligible → Proceed to step 3

3. Consider locoregional therapies for patients with localized disease:

   • TACE for intermediate stage or selected advanced cases
   • SIRT for patients without extrahepatic disease
   • HAIC for selected patients

4. Upon progression on first-line therapy:

   • After sorafenib → Consider regorafenib, cabozantinib, or ramucirumab (if AFP ≥400 ng/mL)
   • After other first-line therapies → Consider cabozantinib or immunotherapy options

Important Considerations

• Liver function assessment is crucial before starting any systemic therapy, as most options require Child-Pugh A liver function
• Regular monitoring for treatment response using dynamic CT or MRI studies with mRECIST criteria is recommended 1
• Adverse event management is essential for maintaining patients on therapy at effective doses
• Clinical trials should be considered when available, as the landscape of HCC treatment is rapidly evolving

The selection of therapy should be guided by the patient's liver function, performance status, extent of disease, and specific contraindications to available treatments, with the goal of maximizing survival while maintaining quality of life.