Nahon P, Ziol M, Pan L, Portal JJ, Oberti F, Aube C, Blanc JF, Trillaud H, Merle P, Rode A, Assenat E, Guiu B, Lequoy M, Cornelis F, Bouattour M, Talib Z, Tibi A, Zeng Q, Bouda Y, Ganne-Carrié N, Sutter O, Sutton A, Guyot E, Barget N, Zucman-Rossi J, Campani C, Bamba-Funck J, Calderaro J, Nault JC, Vicaut E, Seror O.
Hepatology. 2026 Apr 8.
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 pathological response. Circulating protein variations were associated with pathological or radiological responses and local recurrence.
Conclusions: Neoadjuvant and adjuvant nivolumab in BCLC A HCC patients eligible for IRE lead to pathological response related to immune activation and show anti-tumoral effect.
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