What are the contraindications for lenvatinib (Lenvima) and sorafenib (Nexavar) in hepatocellular carcinoma (HCC)?

Contraindications for Lenvatinib and Sorafenib in Hepatocellular Carcinoma

For patients with hepatocellular carcinoma (HCC), lenvatinib is contraindicated in those with main portal vein invasion, while sorafenib is contraindicated in patients with clinically symptomatic vascular disease (either coronary or peripheral).

General Contraindications for Both Medications

Liver Function

• Child-Pugh B/C liver dysfunction: Both medications are primarily indicated for patients with preserved liver function (Child-Pugh A) 1, 2
• Severe hepatic impairment: Risk of hepatotoxicity increases with compromised liver function 3

Performance Status

• Poor performance status: Both medications are indicated for patients with ECOG PS 0-1 1, 2
• Severely compromised functional status: Patients with ECOG PS ≥2 are generally not suitable candidates 1

Specific Contraindications for Lenvatinib

1. Main portal vein invasion 1, 2

   • Lenvatinib has not been studied in this population
   • Safety and efficacy cannot be guaranteed

2. Tumor occupying >50% of liver volume 2

   • Excluded from pivotal clinical trials
   • Higher risk of adverse events

3. Bile duct invasion 2

   • Excluded from pivotal clinical trials
   • Risk of biliary complications

4. Cardiac dysfunction 3

   • Monitor for clinical symptoms or signs of cardiac dysfunction
   • Withhold for Grade 3 and discontinue for Grade 4 cardiac dysfunction

5. Arterial thromboembolic events 3

   • Discontinue following an arterial thromboembolic event

Specific Contraindications for Sorafenib

1. Clinically symptomatic vascular disease 1

   • Either coronary or peripheral vascular disease
   • Considered a formal contraindication

2. Severe renal impairment 3

   • Increased risk of adverse events
   • Dose adjustments may be required

Common Adverse Events to Consider

Lenvatinib

• Hypertension (42%) 2, 3
• Diarrhea (39%) 3
• Decreased appetite/weight (34%/31%) 3
• Proteinuria (25%) 3
• Hand-foot skin reaction (27%) 3

Sorafenib

• Hand-foot skin reaction (52%) 1
• Diarrhea (45%) 1
• Hypertension (30%) 1

Monitoring Requirements

1. Before initiating therapy:

   • Confirm Child-Pugh A liver function
   • Verify ECOG PS 0-1
   • For lenvatinib: confirm absence of main portal vein invasion
   • For sorafenib: confirm absence of symptomatic vascular disease

2. During treatment:

   • Regular blood pressure monitoring 2, 4
   • Liver function tests 3
   • Urinalysis for proteinuria 2, 3
   • Thyroid function tests 2, 3
   • Monitor for gastrointestinal symptoms 3

Special Considerations

• Relative contraindications: In patients with Child-Pugh B, sorafenib may be used with caution, but survival benefit is more pronounced in Child-Pugh A patients 1
• Treatment duration: Median treatment duration is approximately 5-6 months for both medications 1, 3
• Dose adjustments: Approximately 35% of patients on sorafenib require dose reductions 1
• Adverse event management: Proactive management of adverse events is crucial to maintain patients on therapy at effective doses 4

Alternative Treatment Options

When both lenvatinib and sorafenib are contraindicated, consider:

• Atezolizumab plus bevacizumab (first-line option) 1, 2
• Regorafenib, cabozantinib, or ramucirumab (second-line options) 1

By carefully assessing these contraindications before initiating therapy, clinicians can optimize treatment selection and minimize the risk of serious adverse events in patients with HCC.