Cui Xiaowen, Ruan Minghao, Li Yao, Yang Cheng, Zhang Jin, Jin Riming, Wu Dong, Sun Wen, Wang Ruoyu
Department of Oncology, Eastern Hepatobiliary Surgery Hospital, The Naval Medical University, Shanghai, China.
The First Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Naval Medical University, 225 Changhai Road, Shanghai, 200438, China.
Cancer Immunol Immunother. 2025 Jun 7;74(8):239. doi: 10.1007/s00262-025-04089-x.
Resistance limits the efficacy and durability of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). Therefore, we conducted a retrospective cohort study to investigate the outcomes and characteristics of HCC patients with resistance to immunotherapy. Patients with HCC who have received ICIs at Eastern Hepatobiliary Surgery Hospital between 2016 and 2021 were retrospectively screened and divided into primary resistance, secondary resistance, and durable response group. Time to progression (TTP), overall survival (OS), subsequent management and post-progression survival (PPS) were analyzed. Of 496 patients included, 229 (46.2%) and 141 (28.4%) patients developed primary and secondary resistance, and 126 (25.4%) patients achieved a durable response, the median TTP was 2.83 [2.56-3.09] months, 11.93 [10.45-13.40] months, and not reached, respectively, whereas the median OS was 12.83 [10.36-15.30] months, 31.53 [28.09-34.97] and not reached, respectively. Multivariate logistic regression revealed that Child-Pugh score, BCLC stage, and combined systemic therapies (ICI plus bevacizumab or lenvatinib versus ICI monotherapy) were independently associated with primary resistance, and only combined systemic therapies (ICI plus bevacizumab versus ICI monotherapy) were independently associated with secondary resistance. AFP levels were independently associated with PPS in patients with primary resistance, while post-progression therapies (ICI-based therapies versus others) were independently associated with PPS in patients with resistance. The risk of resistance was notably lower in patients receiving the combination of ICI plus bevacizumab. High AFP levels were associated with the survival of patients with primary resistance. ICI-based maintenance therapy after resistance may provide a significant survival advantage for HCC patients.
耐药性限制了免疫检查点抑制剂（ICI）在肝细胞癌（HCC）中的疗效和持久性。因此，我们进行了一项回顾性队列研究，以调查对免疫治疗耐药的HCC患者的预后和特征。对2016年至2021年期间在东方肝胆外科医院接受ICI治疗的HCC患者进行回顾性筛选，并分为原发性耐药、继发性耐药和持久缓解组。分析了疾病进展时间（TTP）、总生存期（OS）、后续治疗及进展后生存期（PPS）。在纳入的496例患者中，229例（46.2%）和141例（28.4%）患者发生原发性和继发性耐药，126例（25.4%）患者获得持久缓解，TTP的中位数分别为2.83[2.56-3.09]个月、11.93[10.45-13.40]个月和未达到，而OS的中位数分别为12.83[10.36-15.30]个月、31.53[28.09-34.97]个月和未达到。多因素逻辑回归显示，Child-Pugh评分、BCLC分期和联合全身治疗（ICI联合贝伐单抗或仑伐替尼与ICI单药治疗）与原发性耐药独立相关，仅联合全身治疗（ICI联合贝伐单抗与ICI单药治疗）与继发性耐药独立相关。AFP水平与原发性耐药患者的PPS独立相关，而进展后治疗（基于ICI的治疗与其他治疗）与耐药患者的PPS独立相关。接受ICI联合贝伐单抗治疗的患者耐药风险显著较低。高AFP水平与原发性耐药患者的生存相关。耐药后基于ICI的维持治疗可能为HCC患者提供显著的生存优势。
