Neoadjuvant and adjuvant nivolumab associated with irreversible electroporation in patients with early hepatocellular carcinoma and high risk of recurrence (NIVOLEP trial)

作者：Pierre Nahon, M. Ziol, Long Pan, Jean-Jacques Portal, Frédéric Oberti, C. Aubé, Jean-Frederic Blanc, Hervé Trillaud, Philippe Merle, A.M. Rode, Eric Assenat, Boris Guiu, Marie Lequoy, F Cornélis, Mohamed Bouattour, Zohra Talib, ANNICK R. TIBI, Qinghe Zeng, Yasmine Bouda, Nathalie Ganne-Carrié, Olivier Sutter, Angela Sutton, E. Guyot, Nathalie Barget, Jessica Zucman-Rossi, Claudia Campani, Jessica Bamba-Funck, Julien Caldéraro, Jean-Charles Nault, E. Vicaut, Olivier Séror · 发表于：Hepatology · 年份：2026 · DOI：10.1097/hep.0000000000001764 · 被引用次数：1 · 研究领域：Microbial Inactivation Methods、Hepatocellular Carcinoma Treatment and Prognosis、Ultrasound and Hyperthermia Applications

BACKGROUND AND AIMS: Irreversible electroporation (IRE) is a non-thermal ablation technique suited for difficult-to-treat hepatocellular carcinoma (HCC) with 1-year local recurrence (LR) rates above 50%. We hypothesized that peri-procedural immunotherapy could synergize with IRE to decrease local recurrence. APPROACH AND RESULTS: NIVOLEP is a multicenter phase 2 trial evaluating nivolumab combined with IRE in patients with BCLC A HCC. Patients received 2 neoadjuvant nivolumab infusions, IRE with curative intent, and 12 monthly adjuvant nivolumab infusions. Tumor biopsies were performed at baseline and during IRE. The primary endpoint was 1-year local recurrence-free survival (LRFS). In all, 62 HCC nodules (mean size: 30.0 mm) from 43 patients (mean age: 71 y, 88% male, 81% cirrhosis) were considered. All patients received neoadjuvant nivolumab; 35 underwent curative IRE (8 others: 4 IRE failures, 3 HCC progressions, 1 death). After neoadjuvant nivolumab, radiological or pathological response was observed in 24.2% and 26.3% nodules, respectively. One-year LRFS was 70.6% (95% CI: 55.3-85.9), and 2-year overall survival was 74.2% in the intention-to-treat analysis. Grade 3 or 4 adverse events related to nivolumab occurred in 2 patients; 1 patient died due to nivolumab. RNA-sequencing analysis of the tumor after neoadjuvant nivolumab showed an enrichment of pathways associated with leukocyte migration, T cell activation, and CD8+ T and B-cell infiltration associated with patholog...