What is the recommended treatment approach for patients with intermediate or advanced hepatocellular carcinoma (HCC) using Transarterial Chemoembolization (TACE) plus Lenvatinib (levatinib)?

TACE Plus Lenvatinib for Hepatocellular Carcinoma

For intermediate-stage HCC beyond up-to-seven criteria with Child-Pugh A liver function, TACE combined with lenvatinib is superior to TACE alone, achieving median OS of 28 months versus 12 months and should be the preferred treatment approach. 1

Patient Selection for TACE Plus Lenvatinib

Ideal candidates for this combination therapy include:

• Intermediate-stage HCC (BCLC-B) beyond up-to-seven criteria with large or multinodular tumors 2
• Child-Pugh A liver function (mandatory requirement, as lenvatinib has limited data in Child-Pugh B or C) 2, 3
• ECOG performance status 0-1 4
• No main portal vein invasion, clear bile duct invasion, or >50% liver volume tumor occupancy 2
• Preserved liver function without ascites 2

The 2025 EASL guidelines specifically note that lenvatinib can be considered as initial treatment in intermediate-stage HCC beyond up-to-seven criteria with Child-Pugh A function 2, and this approach was approved by the Asia-Pacific Primary Liver Cancer Expert Association 2.

Treatment Efficacy Data

The combination demonstrates substantial clinical benefits over TACE monotherapy:

• Objective response rate: 94% versus 47% with TACE alone 1
• Disease control rate: 97% versus 62% with TACE alone 1
• Median progression-free survival: 8.2-8.9 months versus 3.7 months 1
• Median overall survival: 28 months versus 12 months 1

Broader literature reviews show lenvatinib plus TACE achieves ORRs of 53.1%-75%, median PFS of 6.15-11.6 months, and median OS of 14.5-18.97 months across various studies 5.

Treatment Protocol

Lenvatinib dosing:

• Administer lenvatinib orally once daily at standard dosing (12 mg for patients ≥60 kg, 8 mg for patients <60 kg) 4
• Continue lenvatinib continuously between TACE sessions 5

TACE administration:

• Perform TACE using either conventional TACE or drug-eluting beads (both are acceptable standards) 2
• Repeat TACE "on-demand" with 1-2 month intervals between sessions 6
• Ensure superselective catheterization to minimize liver injury 6

Response assessment:

• Evaluate response at 4-6 weeks post-TACE using CT or MRI with mRECIST criteria 6
• Continue imaging every 6-8 weeks during treatment 7

Critical Contraindications

Absolute contraindications for this combination include:

• Decompensated cirrhosis (Child-Pugh C or decompensated Child-Pugh B) 6
• Complete main portal vein occlusion (contraindication for TACE specifically) 6
• ECOG performance status ≥2 6
• Obstructive jaundice or advanced liver dysfunction 6
• Advanced kidney dysfunction 2
• Extrahepatic spread (relative contraindication for TACE) 2

When to Stop TACE and Continue Lenvatinib Alone

Discontinue TACE but may continue lenvatinib if:

• No radiological response after 2-3 TACE sessions 6
• Liver function deteriorates (development of Child-Pugh B or worsening ascites) 6
• Development of TACE failure/refractoriness 2
• Likely to develop Child-Pugh class B liver function after next TACE 2

The concept of "unsuitable TACE" includes patients who exceed up-to-seven criteria, have mALBI grade 2b liver function, or have HCC other than simple nodular type 2. For these patients, upfront systemic therapy with lenvatinib alone may be preferable 2.

Monitoring Requirements

Liver function surveillance:

• Monitor liver function tests every 2-4 weeks during the first 2 months 3
• Watch for signs of hepatic decompensation including worsening ascites, encephalopathy, or rising bilirubin 3

Safety profile:

• The combination does not increase grade 3-4 adverse events compared to TACE alone 1
• Most adverse events are manageable 5
• The combination shows a trend toward improving liver function rather than worsening it 1

Alternative Considerations

For patients with portal vein tumor thrombus (PVTT):

• Lenvatinib plus TACE is superior to sorafenib plus TACE 5
• Consider adding PD-1 inhibitors (triple therapy) for patients with main PVTT, achieving ORRs of 46.7%-80.6% and median OS of 16.9-24 months 5

Important caveat: The 2024 British Society of Gastroenterology guidelines state that TACE should not be combined with multikinase inhibitors outside of clinical trials, and there is insufficient evidence to recommend TACE with immune checkpoint inhibitors 2. However, this recommendation predates the 2024 propensity-matched analysis showing clear survival benefit 1, and conflicts with Asian practice patterns where this combination has been adopted 2.

Common Pitfalls to Avoid

• Do not perform extensive TACE with massive chemo-embolic materials for more than half of the liver, as this significantly increases post-procedural liver failure risk 6
• Do not continue TACE indefinitely without response assessment; switch to systemic therapy after 2-3 failed sessions to preserve liver function 6, 8
• Do not use this combination in Child-Pugh B or C patients due to lack of safety data for lenvatinib in these populations 3
• Do not delay treatment switch in patients showing TACE refractoriness, as early switch to systemic therapy preserves liver function for sequential therapies 8