What are the considerations for lenvatinib (generic name) treatment in patients with hepatocellular carcinoma (HCC)?

Considerations for Lenvatinib Treatment in Hepatocellular Carcinoma

Lenvatinib is recommended as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) who have preserved liver function (Child-Pugh A) and good performance status (ECOG 0-1), but should not be used in patients with main portal vein invasion. 1

Patient Selection Criteria

Required Baseline Characteristics:

• Child-Pugh A liver function (essential requirement) 1
• ECOG performance status 0-1 1
• No main portal vein invasion 1
• Tumor not occupying >50% of liver volume 1
• No bile duct invasion 1

Contraindications:

• Child-Pugh B or C liver function 1
• Main portal vein invasion 1
• Clinically symptomatic vascular disease (coronary or peripheral) 1

Dosing Considerations

• Weight-based dosing:
  • 12 mg once daily for patients ≥60 kg
  • 8 mg once daily for patients <60 kg 2
• Take orally once daily until disease progression or unacceptable toxicity 2
• Maintaining optimal relative dose intensity (≥67% at 8 weeks) is associated with better response and survival 3

Efficacy Profile

• Non-inferior to sorafenib for overall survival (13.6 vs 12.3 months) 1
• Superior to sorafenib in:
  • Progression-free survival (7.4 vs 3.7 months) 1
  • Time to progression (8.9 vs 3.7 months) 1
  • Objective response rate (24% vs 9.2% by mRECIST) 1

Adverse Event Management

Common Adverse Events to Monitor:

1. Hypertension (42%) - most common serious adverse event 1, 4
2. Diarrhea (39%) 1, 4
3. Decreased appetite/weight (34%/31%) 1, 4
4. Proteinuria (25%) 1, 2, 4
5. Hand-foot skin reaction (27%) - less frequent than with sorafenib (54%) 1, 4
6. Fatigue (30%) 1, 4
7. Hypothyroidism (16%) 1
8. Hepatotoxicity - monitor liver function tests 2

Monitoring Requirements:

• Blood pressure - regular monitoring, especially early in treatment 4
• Urinalysis - monitor for proteinuria 2
  • If dipstick shows ≥2+ protein, check urine protein/creatinine ratio
  • If 24-hour urinary protein ≥2g, interrupt treatment 1
• Thyroid function - monitor TSH levels 1
  • Consider endocrinology consultation if TSH >10 mIU/L or >5 mIU/L on two separate occasions
• Liver function tests - every 2 weeks for first 2 months, then monthly 2
• Regular assessment for hand-foot skin reaction 4

Dose Modification Strategy:

• For Grade 1-2 adverse events: generally continue treatment with supportive care 4
• For persistent/intolerable Grade 2 or Grade 3 events: 4
  • Interrupt treatment until symptoms improve to Grade 0-1
  • Resume at same or reduced dose
• For Grade 4 events: discontinue permanently 2
• Aim to maintain highest possible dose to maximize efficacy 4

Treatment Sequencing

• First-line options for advanced HCC:

  • Atezolizumab plus bevacizumab (preferred first choice per recent guidelines) 5
  • Lenvatinib (alternative first-line option) 1, 5
  • Sorafenib (alternative first-line option) 1, 5

• After lenvatinib progression, options include: 1

  • Sorafenib
  • Regorafenib
  • Cabozantinib
  • Ramucirumab (if AFP ≥400 ng/mL)
  • Immune checkpoint inhibitors (atezolizumab-bevacizumab, durvalumab-tremelimumab, pembrolizumab, nivolumab-ipilimumab)

Combination Approaches

Emerging evidence suggests potential benefits of combining lenvatinib with:

• Transarterial chemoembolization (TACE) - improved overall survival compared to lenvatinib alone (17.8 vs 11.5 months) 6
• Immunotherapy plus hepatic arterial infusion chemotherapy - promising results in early studies 7

Special Considerations

• Patients who place higher value on delayed radiologic disease progression may prefer lenvatinib over sorafenib 1
• Patients concerned about skin reactions may prefer lenvatinib (lower incidence of hand-foot skin reaction than sorafenib) 1
• Patients with hypertension may prefer sorafenib (lower incidence of hypertension) 1
• Development of hypertension during treatment may be associated with better prognosis 1