Adding Lenvatinib plus Pembrolizumab to Transarterial Chemoembolization for Hepatocellular Carcinoma

Immunotherapy combinations, including tremelimumab plus durvalumab, ipilimumab plus nivolumab, and atezolizumab plus bevacizumab, have demonstrated superiority over tyrosine kinase inhibitors (TKIs) in the treatment of advanced hepatocellular cancer (HCC) and are considered first-line therapy in that setting. In liver-confined HCC, the addition of single-agent TKIs to regional therapy has led to mixed and largely negative results compared with regional therapy alone.

Investigators now report results from the LEAP-012 trial, an industry-sponsored, global, phase 3 study in which patients with unresectable nonmetastatic HCC were randomized to receive transarterial chemoembolization (TACE) in combination with either lenvatinib plus pembrolizumab (LP) or dual placebo. TACE (whether conventional or with drug-eluting beads) was limited to two treatments per tumor. Of the 480 study participants, 72% were Asian, and the cause of HCC was hepatitis B in 62%, alcohol in 46%, and hepatitis C in 17%.

Progression-free survival was significantly better with LP than with placebo (median, 14.6 vs. 10.0 months; hazard ratio; 0.66; P=0.0002), as was objective response rate (47% vs. 33%; P=0.0005). However, no significant difference was seen in overall survival (HR; 0.80, P=0.087), which, at 24 months, was 75% for the LP group and 69% for the placebo group. Grade 3/4 treatment-related serious adverse events occurred in 71% of the LP group compared with 32% of the placebo group.