Adding Lenvatinib Plus Pembrolizumab to TACE Improves Survival in Intermediate-Stage Hepatocellular Cancer

Nov 11, 2024

Photo Credit: Mohammed Haneefa Nizamudeen

Treatment with lenvatinib plus pembrolizumab in combination with transarterial chemoembolisation (TACE) was superior to TACE alone in patients with intermediate-stage hepatocellular cancer (HCC) who are not amenable to curative treatment, first results of LEAP-012 study demonstrated.

For decades, the standard treatment of intermediate-stage hepatocellular carcinoma (HCC) is TACE; however, survival has been modest (median overall survival 26–30 months)^1,2. Lenvatinib is a first-line treatment option for patients with unresectable HCC who are ineligible for TACE or refractory to TACE³. In the previous LEAP-002 study, first-line lenvatinib plus pembrolizumab showed a trend for prolonged overall survival (OS), compared with lenvatinib alone in patients with advanced HCC⁴.

The ongoing, randomized, phase 3 LEAP-012 trial (NCT04246177) aimed to evaluate the efficacy and safety of lenvatinib plus pembrolizumab in combination with TACE versus TACE alone in patients with intermediate-stage HCC. LEAP-012 enrolled 480 participants with confirmed HCC not amenable to curative treatment and with greater than or equal to one measurable lesion were randomly assigned to receive lenvatinib plus pembrolizumab plus TACE or dual placebo plus TACE. The primary endpoints were PFS and OS. Josep Llovet, MD, PhD, from the Icahn School of Medicine at Mount Sinai, in New York presented the results of the first interim analysis⁵.

After a median follow-up of 25.6 months, the median PFS in the lenvatinib/pembrolizumab arm was 14.6 (95% CI 12.6–16.7) months versus 10.0 (95% CI 8.1–12.2) in the placebo arm (HR 0.66; 95% CI 0.51–0.84; P=0.0002). PFS rate at 18 months was 39.1% versus 27.9%. Lenvatinib plus pembrolizumab also numerically favored OS rate at 24 months over placebo: 74.6% versus 68.6% (HR 0.80; 95%CI 0.57–1.11; P=0.867).

In addition, the objective response rate (ORR) was significantly (P<0.0001) higher in the lenvatinib/pembrolizumab arm; 71.3% (95% CI 65.1–77.0) versus 49.8% (95% CI 43.3–56.3), as was the median duration of response (14.6 months vs 12.5 months).

Grade 3 or 4 AEs were more common in the lenvatinib/pembrolizumab arm than the placebo arm (71.3% vs 31.1%), as was treatment discontinuation (8.4% vs 1.2%).

Based on these outcomes, Prof. Llovet concluded that “treatment with lenvatinib plus pembrolizumab plus TACE may be a new option for patients with intermediate-stage HCC.”

Medical writing support was provided by Marten Dooper.