The combination of pembrolizumab and lenvatinib is no more effective than lenvatinib alone in patients with advanced hepatocellular carcinoma (HCC), according to research presented at ESMO Congress 2022.

Researchers found that adding pembrolizumab to lenvatinib did not provide a significant improvement in progression-free survival (PFS) or overall survival (OS) in the phase 3 LEAP-002 trial

The LEAP-002 trial ( Identifier: NCT03713593) included 794 patients who had received no prior systemic therapy for advanced HCC and were not amenable to curative therapy.

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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 arms. The median age in both arms was 66 years (overall range, 19-88), and more than 80% of patients were men.

The patients were treated until disease progression, intolerable toxicity, or patient withdrawal. Pembrolizumab or placebo could be given for a maximum of 35 cycles.

The co-primary endpoints were OS and PFS. The median follow-up for PFS was 17.6 months, and the median follow-up for OS was 32.1 months.

The median OS was 21.2 months in the pembrolizumab arm and 19.0 months in the placebo arm (hazard ratio [HR], 0.840; 95% CI, 0.708-0.997; P =.0227). This did not meet the prespecified threshold for superiority. The 24-month OS rate was 43.7% with pembrolizumab and 40.0% with placebo.

The median PFS was 8.2 months in the pembrolizumab arm and 8.0 months in the placebo arm (HR, 0.867; 95% CI, 0.734-1.024; P =.0466). Again, the prespecified threshold for superiority was not met.

According to RECIST 1.1 criteria, the objective response rate was 26.1% in the pembrolizumab arm and 17.5% in the placebo arm. The median duration of response was 16.6 months and 10.4 months, respectively.

Grade 3-4 treatment-related adverse events (TRAEs) occurred in 61.5% of patients in the pembrolizumab arm and 56.7% of those in the placebo arm. The most common grade 3-4 TRAEs in the pembrolizumab arm were hypertension, AST elevation, diarrhea, and proteinuria. 

Fatal TRAEs in the pembrolizumab arm included hepatic encephalopathy (n=2), hepatorenal syndrome (n=1), and gastrointestinal hemorrhage (n=1). Fatal TRAEs in the lenvatinib arm included cerebrovascular accident (n=1), hepatorenal syndrome (n=1), and gastrointestinal hemorrhage (n=1).

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


Finn RS, Kudo M, Merle P, et al. Primary results from the phase III LEAP-002 study: Lenvatinib plus pembrolizumab versus lenvatinib as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC). Presented at ESMO 2022; September 9-13, 2022. Abstract LBA34.