Lenvatinib plus pembrolizumab added to transarterial embolization in hepatocellular carcinoma

Results from the phase III LEAP-012 trial, recently published on The Lancet, show a clinically meaningful improvement in progression-free survival in patients with unresectable, non-metastatic hepatocellular carcinoma treated by adding lenvatinib plus pembrolizumab to the standard care with transarterial embolization (TACE).

LEAP-012 is a multicentre, randomised, double-blind, phase 3 study where 480 patients with unresectable, non- metastatic hepatocellular carcinoma not amenable to curative treatment were randomly assigned to receive TACE plus lenvatinib plus pembrolizumab or TACE plus dual placebo. At the data cutoff for this interim analysis, median follow-up was 25.6 months. Median progression-free survival was 14.6 months with lenvatinib plus pembrolizumab and 10 months with placebo; 24-month overall survival rate was 75% and 69% respectively. Grade 3 or worse treatment-related adverse events occurred in 71% of 237 participants in the lenvatinib plus pembrolizumab group and in 32% of 241 in the placebo group, the most common of which were hypertension and platelet count decreased.  Overall survival data are immature, although promising, and as authors point out, «The target patient population of the study reflects an area of medical unmet need, which includes patients with unresectable, non-metastatic hepatocellular carcinoma and those with early-stage disease unsuitable for potentially curative therapies. Previous studies have not consistently shown a survival benefit when other systemic therapies are added to treatment with TACE: although longer follow-up is necessary to definitively identify whether there is a survival benefit, these first interim results from LEAP-012 support the use of lenvatinib plus pembrolizumab plus TACE compared with transarterial embolization alone in this setting. Based on these data, lenvatinib plus pembrolizumab plus TACE could be a new option for patients with unresectable, non-metastatic hepatocellular carcinoma», authors conclude.