TACE with lenvatinib + pembrolizumab prolongs PFS in unresectable HCC

In the treatment of patients with unresectable, nonmetastatic hepatocellular carcinoma (HCC), adding lenvatinib plus pembrolizumab to transarterial chemoembolization (TACE) results in clinically meaningful improvement in progression-free survival (PFS), according to data from the phase III LEAP-012 study.

LEAP-012 included 480 adults (median age 66 years, 83 percent male, 72 percent Asian) with unresectable, nonmetastatic HCC amenable to TACE but not curative treatment. These patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and Child-Pugh class A disease.

The patients were randomly assigned to receive TACE with either oral lenvatinib (once daily at 12 mg for those with bodyweight ≥60 kg or 8 mg for those with bodyweight <60 kg) plus intravenous pembrolizumab (400 mg once every 6 weeks for up to 2 years) or matched dual placebo (oral and intravenous).

Primary endpoints were PFS and overall survival (OS) in the intention-to-treat population (TACE plus lenvatinib plus pembrolizumab n=237; TACE plus dual placebo n=243). Safety was evaluated in the as-treated population.

Over a median follow-up of 25.6 months, the median PFS was 14.6 months (95 percent confidence interval [CI], 12.6–16.7) with lenvatinib plus pembrolizumab and 10.0 months (95 percent CI, 8.1–12.2). Lenvatinib plus pembrolizumab was associated with a 34-percent reduction in the risk of progression or death compared with placebo (hazard ratio [HR], 0.66, 95 percent CI, 0.51–0.84; one-sided p=0.0002).

In terms of OS, 29 percent of patients in the lenvatinib plus pembrolizumab group and 34 percent in the placebo group died, with a 24-month OS rate of 75 percent (95 percent CI, 68–80) and 69 percent (95 percent CI, 62–74), respectively. The difference was not statistically significant (HR, 0.80, 95 percent CI, 0.57–1.11; p=0.087).

Grade 3 or worse treatment-related adverse events (TRAEs) were documented in 71 percent of patients in the lenvatinib plus pembrolizumab group and in 32 percent in the placebo group. The most common TRAEs were hypertension (24 percent vs 7 percent) and reduced platelet count (11 percent vs 6 percent). TRAEs led to death in four patients in the lenvatinib plus pembrolizumab group and in one in the placebo group.