Journal Article

Stereotactic body radiotherapy with sintilimab and bevacizumab biosimilar in anti-PD-1 refractory hepatocellular carcinoma: the ReUNION-1 phase 2 trial

Yang, Yongqiang, Liu, Dongen, Wang, Bicheng, Chen, Lei, Liu, Yaqin, Zhang, Dejun, Ge, Minghui, Zhang, Jinfeng, Xue, Jun, Tang, Jing, Wu, Zilong, Lin, Zhenyu, Wu, Gang, Zhang, Tao

2025

Overview

Immune checkpoint inhibitor (ICI) resistance in hepatocellular carcinoma (HCC) poses a major therapeutic challenge. Here we present a Phase 2 trial evaluating stereotactic body radiotherapy (SBRT) combined with sintilimab and bevacizumab biosimilar (PD-1/VEGF blockade) to overcome resistance in ICI-refractory HCC. Twenty-one patients with progressive HCC after ICI therapy receive SBRT followed by sintilimab 200 mg and bevacizumab biosimilar 15 mg/kg every 3 weeks. The primary outcome, objective response rate in non-irradiated lesions is 33.3%, with a disease control rate of 66.7%. Median progression-free survival is 6.2 months, and estimated median overall survival is 24.4 months. SBRT achieves 100% local control, with 33.3% experiencing grade 3 or higher adverse events. Proteomic profiling reveals that responders exhibit lower baseline IFN-γ and elevated IL-6, while post-SBRT increases in IFN-γ, IL-2, and IL-6 correlate with improved outcomes. These results indicate that combination of SBRT in ICI-refractory HCC is effective, well-tolerated, and may be guided by cytokine assessment. Immune checkpoint inhibitor resistance limits treatment options in advanced hepatocellular carcinoma. Here, the authors report a Phase 2 trial of stereotactic body radiotherapy combined with PD-1/VEGF blockade in patients with refractory hepatocellular carcinoma.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 692/4028/67/1059/2325 / 692/4028/67/1059/485 / 692/4028/67/1504/1610/4029 / 82/1 / 82/51 / 82/80 / Adult / Aged / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Bevacizumab / Bevacizumab - administration & dosage / Bevacizumab - therapeutic use / Biological products / Biosimilar Pharmaceuticals - administration & dosage / Biosimilar Pharmaceuticals - therapeutic use / Cancer therapies / Carcinoma, Hepatocellular - drug therapy / Carcinoma, Hepatocellular - mortality / Carcinoma, Hepatocellular - radiotherapy / Carcinoma, Hepatocellular - therapy / Combined Modality Therapy / Cytokines / Disease control / Drug Resistance, Neoplasm / Female / Hepatocellular carcinoma / Humanities and Social Sciences / Humans / Immune checkpoint inhibitors / Immune Checkpoint Inhibitors - therapeutic use / Immunotherapy / Inhibitors / Interleukin 6 / Lesions / Liver cancer / Liver Neoplasms - drug therapy / Liver Neoplasms - mortality / Liver Neoplasms - radiotherapy / Liver Neoplasms - therapy / Male / Middle Aged / multidisciplinary / Oncology / Patients / PD-1 protein / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Progression-Free Survival / Proteomics / Radiation therapy / Radiosurgery - adverse effects / Radiosurgery - methods / Response rates / Science / Science (multidisciplinary) / Survival / Treatment Outcome / Tumors / Vascular endothelial growth factor / γ-Interferon