# LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma

Source: https://onco.cc/key-papers/paper-leap-012-lancet-2025/  
OnCo record `paper-leap-012-lancet-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding lenvatinib and pembrolizumab to chemoembolisation delayed progression in intermediate-stage liver cancer, the second trial to show that systemic therapy improves on embolisation alone, at the cost of more side effects.

## Summary

Phase 3 placebo-controlled trial of 480 patients with unresectable, non-metastatic hepatocellular carcinoma suitable for chemoembolisation randomised to transarterial chemoembolisation with lenvatinib plus pembrolizumab or with dual placebo.

Median progression-free survival was 14.6 versus 10.0 months (hazard ratio 0.66), with an early trend in overall survival (hazard ratio 0.80, not significant) and grade 3 to 4 treatment-related adverse events of 71 versus 32 percent.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: The Lancet
- Year: 2025
- DOI: 10.1016/S0140-6736(24)02575-3
- Authors: Kudo M, Ren Z, Guo Y, et al.
- Findings: Median progression-free survival 14.6 vs 10.0 months; hazard ratio 0.66.; Grade 3 to 4 treatment-related adverse events 71 percent vs 32 percent.
- What it means: Lenvatinib-pembrolizumab with chemoembolisation is an emerging option for intermediate-stage disease, balanced against substantial toxicity.
- Caveats: Overall survival not yet significant.; High toxicity may limit uptake.

## Sources

- Lancet 2025: https://doi.org/10.1016/S0140-6736(24)02575-3
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39798578/

## Connected records

- cancers: [Intermediate hepatocellular carcinoma (BCLC B)](https://onco.cc/cancers/hcc-intermediate/)
- drugs: [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [LEAP-012](https://onco.cc/trials/leap-012/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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