What are the contraindications for immunotherapy or Lenvatinib (lenvatinib) in patients with hepatocellular carcinoma (HCC)?

Contraindications for Immunotherapy or Lenvatinib in Hepatocellular Carcinoma

Immunotherapy is contraindicated in patients with poor liver reserve, while lenvatinib is contraindicated in patients with poorly-controlled hypertension, high bleeding risk, main portal vein invasion, or clear bile duct invasion. 1

Contraindications for Immunotherapy in HCC

Absolute Contraindications

• Poor liver function (Child-Pugh B8-9 or C) 1
• Active autoimmune disease requiring immunosuppression
• History of severe immune-related adverse events on prior immunotherapy
• Organ transplant recipients on immunosuppressive therapy

Relative Contraindications

• High-grade esophageal varices (Grade 2 or higher) - specifically for atezolizumab plus bevacizumab 2
• Main portal vein invasion - for bevacizumab-containing regimens 2
• Clear bile duct invasion - for bevacizumab-containing regimens 2

Contraindications for Lenvatinib in HCC

Absolute Contraindications

• Poorly-controlled hypertension 1
• High bleeding risk 1
• Main portal vein invasion 2
• Clear bile duct invasion 2
• 50% or more of tumor to total liver volume occupancy 1
• Cardiac dysfunction (Grade 3-4) 3
• Hepatic failure 3
• Nephrotic syndrome 3
• Grade 3-4 fistula or any grade gastrointestinal perforation 3

Relative Contraindications

• Moderate to severe renal impairment 3
• QT interval prolongation (>500 ms) 3
• Recent major surgery (within 2 weeks) 3
• Pregnancy or breastfeeding 3

Monitoring and Management Considerations

For Immunotherapy

• Regular monitoring for immune-related adverse events
• Baseline and periodic liver function tests
• Endoscopic screening for esophageal varices before initiating bevacizumab-containing regimens 2
• Monitor for development of proteinuria

For Lenvatinib

• Regular blood pressure monitoring
• Liver function tests prior to and during treatment 3
• Cardiac function assessment
• Proteinuria monitoring 3
• Thyroid function tests monthly 3
• Electrolyte monitoring, particularly calcium levels 3

Treatment Selection Algorithm

1. Assess liver function:

   • Child-Pugh A: Consider both immunotherapy and lenvatinib options
   • Child-Pugh B7: Consider nivolumab monotherapy or sorafenib 1
   • Child-Pugh B8-9 or C: Avoid both immunotherapy and lenvatinib

2. Evaluate vascular invasion and bleeding risk:

   • If high bleeding risk or poorly-controlled hypertension: Avoid lenvatinib 1
   • If main portal vein invasion: Avoid bevacizumab-containing regimens and lenvatinib 2

3. Consider patient preferences:

   • Preference for oral medication: Consider lenvatinib 1
   • Need to avoid frequent hospital visits: Consider lenvatinib

4. Special considerations:

   • For patients with autoimmune conditions: Avoid immunotherapy, consider lenvatinib
   • For patients with cardiac issues: Avoid lenvatinib, consider immunotherapy if cardiac function permits

Remember that treatment decisions should be based on a thorough assessment of the patient's liver function, comorbidities, and tumor characteristics to maximize efficacy while minimizing adverse events.