Pembrolizumab Does Not Improve Upon Lenvatinib in Advanced HCC

Adding pembrolizumab to first-line treatment with lenvatinib does not improve outcomes in patients with advanced hepatocellular carcinoma (HCC), according to phase 3 data published in The Lancet Oncology.

The study showed that pembrolizumab plus lenvatinib did not significantly improve progression-free survival (PFS) or overall survival (OS) over lenvatinib alone.

These results come from the LEAP-002 trial (ClinicalTrials.gov Identifier: NCT03713593), which included 794 eligible patients with previously untreated, unresectable HCC.

The patients were randomly assigned to receive lenvatinib plus pembrolizumab (n=395) or lenvatinib plus placebo (n=399). Baseline characteristics were well balanced between the treatment arms. The median age was 66 years, and 81% of patients were men.

At a median follow-up of 32.1 months, the median OS was 21.2 months in the pembrolizumab-lenvatinib arm and 19.0 months with lenvatinib alone (hazard ratio [HR], 0.84; 95% CI, 0.71-1.00; P =.023). This was not a statistically significant difference according to prespecified criteria (HR, 0.75; P =.023).

The median PFS per independent review and using RECIST version 1.1 was 8.2 months with the combination and 8.1 months with lenvatinib alone (HR, 0.83; 95% CI, 0.71-0.98). The median PFS by investigator assessment was 8.3 months and 8.2 months, respectively (HR, 0.82; 95% CI, 0.70-0.96). Again, prespecified criteria for statistical significance were not met (HR, 0.70; P =.002).

The researchers suggested that the lack of benefit in the combination arm could be a result of the “substantial” use of effective second-line therapies in this trial and the fact that patients in the lenvatinib-alone arm had longer OS than expected.

“Overall, the results of our control group provide a new benchmark for survival estimates when using single-agent molecular therapies for first-line advanced hepatocellular carcinoma,” the researchers wrote.

Treatment-related adverse events (TRAEs) occurred in 96% of patients in both treatment arms. The most common grade 3 or higher TRAEs (in the combination and monotherapy arms, respectively) were hypertension (17% vs 17%), increased aspartate aminotransferase (7% vs 4%), and diarrhea (6% vs 4%).

There were 4 treatment-related deaths in the combination arm (gastrointestinal hemorrhage, hepatorenal syndrome, and 2 cases of hepatic encephalopathy). And there were 3 treatment-related deaths in the monotherapy arm (cerebrovascular accident, gastrointestinal hemorrhage, and hepatorenal syndrome).

Disclosures: This research was supported by Eisai US and Merck Sharp & Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Llovet JM, Kudo M, Merle P, et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): A randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24:1399–1410. doi:10.1016/S1470-2045(23)00469-2

This article originally appeared on Cancer Therapy Advisor