Is there evidence for combining Transarterial Chemoembolization (TACE) and Tyrosine Kinase Inhibitors (TKI) for treating patients with hepatocellular carcinoma (HCC)?

TACE Combined with TKI for HCC: Current Evidence and Recommendations

The combination of TACE with TKIs should NOT be routinely used for intermediate-stage HCC with large tumor burden, as the most recent and highest-quality guideline evidence from EASL 2025 provides a strong recommendation against this practice. 1

Guideline-Based Recommendations

For Intermediate-Stage HCC

• The European Association for the Study of the Liver (EASL) 2025 guidelines explicitly state that intra-arterial therapy (TACE/TAE or SIRT) should NOT be combined with systemic therapy using TKIs in patients with intermediate-stage HCC and large tumor burden (Level of Evidence 2, strong recommendation with 82% consensus). 1

• This strong recommendation against combination therapy represents the most current expert consensus, superseding earlier exploratory approaches that suggested potential benefits. 1

• TACE/TAE should be preferred as monotherapy for liver-confined disease when a selective approach is possible (based on low tumor size and number, no infiltrative appearance, and preserved portal flow). 1

For Advanced-Stage HCC with Portal Vein Invasion

• In patients with advanced-stage HCC due to segmental or lobar portal vein invasion but without extrahepatic spread, there is limited data to recommend the combination of EBRT with TKIs over TKIs alone (Level of Evidence 3, weak recommendation). 1

• The NRG/RTOG1112 phase III trial showed that adding SBRT to sorafenib improved overall survival (median 15.8 vs. 12.3 months, HR 0.77), though the study closed early with only 177 of 292 planned patients. 1

Regional Practice Variations

Chinese Clinical Practice

• Despite Western guideline recommendations against combination therapy, Chinese real-life practice emphasizes combining TACE with TKIs for intermediate HCC, with studies showing improved progression-free survival and opportunities for conversion to resection. 1

• Triple therapy combining TACE with TKIs plus PD-1 inhibitors has shown favorable efficacy in controlling tumor progression in Chinese practice, though this approach lacks endorsement from major Western guidelines. 1

• For advanced HCC with portal vein invasion, Chinese clinicians routinely add systemic therapy (sorafenib, lenvatinib, or lenvatinib plus PD-1 antibody) to TACE, demonstrating more favorable tumor control than systemic therapy alone. 1

Middle East and North Africa Consensus

• The Saudi Association for the Study of Liver Diseases and Transplantation recommends using TACE alone compared to sorafenib in combination with TACE for intermediate-stage HCC. 1

Evidence from Recent Research Studies

Multicenter Retrospective Data (2025)

• A recent multicenter study of 286 patients showed that TACE combined with TKI and immune checkpoint inhibitors (ICI) significantly improved outcomes compared to TKI+ICI alone: median PFS 8.4 vs. 4.0 months (p=0.0016) and median OS 14.5 vs. 10.0 months (p<0.0001). 2

• The combination group achieved higher objective response rates (56.7% vs. 21.1%, p=0.002) and disease control rates (84.3% vs. 72.4%, p=0.023). 2

Meta-Analysis Evidence (2023)

• A systematic review of 30 studies (8,246 patients) found that TACE plus TKIs prolonged time to progression (HR 0.72,95% CI 0.65-0.80) and overall survival (HR 0.57,95% CI 0.49-0.67) compared to TACE alone. 3

• However, combination therapy significantly increased adverse events, particularly hand-foot skin reactions (OR 87.17%), diarrhea (OR 18.13%), and hypertension (OR 12.24%). 3

Critical Safety Considerations

Adverse Event Profile

• The combination of TACE with TKIs substantially increases treatment-related toxicity, requiring careful patient selection and monitoring. 3

• Common adverse events include hand-foot skin reactions, diarrhea, hypertension, fatigue, and increased risk of hemorrhage. 1, 3

Liver Function Preservation

• Preservation of liver function is paramount when considering any combination approach, as deterioration in liver function from repeated TACE may preclude benefit from subsequent systemic therapy. 1

• Combination therapy should only be considered in patients with Child-Pugh A liver function and excellent performance status. 1

When TACE Alone is Insufficient

• After 2-3 consecutive TACE treatments without response and with preserved liver function, other therapies should be considered rather than adding TKIs to ongoing TACE. 1

• The American College of Radiology recommends switching to TARE after TACE failure rather than adding systemic therapy. 4

• Systemic therapy with immune checkpoint inhibitor-based combinations should be offered as an alternative to continued TACE in patients with preserved liver function (Child-Pugh A) and ECOG 0-1. 1

Key Clinical Pitfalls to Avoid

• Do not combine TACE with TKIs based solely on promising retrospective data when high-quality guideline evidence recommends against it for intermediate-stage disease. 1

• Avoid extensive TACE covering more than half the liver when considering any combination approach, as this significantly increases post-procedural liver failure risk. 4

• Do not continue TACE beyond 2-3 sessions without radiological response—this represents TACE refractoriness requiring treatment strategy change. 1

• Recognize that insufficient evidence exists for combining intra-arterial therapy with immunotherapy using checkpoint inhibitors, despite emerging data. 1