TACE Added to Lenvatinib Improves Overall Survival in Hepatocellular Carcinoma

Adding regional therapy to systemic agents, such as sorafenib, in the treatment of hepatocellular carcinoma (HCC) has yielded largely negative results compared to systemic therapy alone. With the advent of newer, potentially more effective systemic treatments, interest in studying the addition of regional therapy continues.

Investigators report results from a multicenter, open-label, randomized, phase 3 trial comparing treatment of HCC with the tyrosine kinase inhibitor lenvatinib with or without hepatic transarterial chemoembolization (TACE). Patients eligible to receive TACE could have a single tumor ≤10 cm or multiple tumors (≤10 foci) with <50% liver involvement. Patients were treated with daily lenvatinib (8 or 12 mg, dependent on weight); TACE was administered on day 1, using either an emulsion of lipiodol and an anticancer agent or drug-eluting beads preloaded with a chemotherapy agent, and could be repeated once.

The 338 patients had a median age of approximately 55, and 80% were men; 86% had hepatitis B, 69% had median tumor size ≥5 cm, 71% had macroscopic portal vein invasion, and 56% had extrahepatic tumor spread.

At a median follow-up of 17 months, the primary endpoint of overall survival was improved with TACE/lenvatinib compared to lenvatinib alone (median, 17.8 vs. 11.5 months; hazard ratio, 0.45; P<0.001). Progression-free survival was also superior with TACE/lenvatinib versus lenvatinib (median, 10.6 vs. 6.4 months; HR, 0.43; P<0.001). Not surprisingly, response rate was also higher with TACE/lenvatinib (45.9% vs. 20.8%). Grade 3/4 adverse events were more common with TACE and included transaminase elevation and increase in bilirubin.