Kim Jung Sun, Kim Youngun, Kang Beodeul, Kim Ilhwan, Kim Hyeyeong, Lee Won Suk, Hong Jung Yong, Lim Ho Yeong, Kim Han Sang, Kim Chang Gon, Jung Sanghoon, An Chansik, Kim Chan, Chon Hong Jae
Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
CHA University School of Medicine, Seongnam, Korea.
Cancer Med. 2025 Jun;14(11):e70997. doi: 10.1002/cam4.70997.
Immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with advanced hepatocellular carcinoma (HCC). Here, we investigate the organ-specific objective response rate (OSORR) of nivolumab plus ipilimumab (Nivo/Ipi) combination treatment, considering prior ICI exposure, compared with nivolumab (Nivo) monotherapy.
We analyzed 204 lesions from Nivo/Ipi-treated and 305 lesions from Nivo-treated patients with advanced HCC at five referral cancer centers in Korea. Organ-specific response criteria were adopted from Response Evaluation Criteria in Solid Tumors 1.1, according to the indicated sites: the liver, lung, lymph nodes (LNs), and other metastatic sites.
Nivo/Ipi combination therapy showed OSORRs of 18.1% in the liver, 17.7% in the lungs, 30.0% in LNs, and 12.5% in other metastatic sites. Patients without prior ICI exposure had OSORRs of 29.0% in the liver, 31.3% in the lungs, 33.3% in LNs, and 23.1% in other metastatic sites (72 individual lesions). Conversely, patients with prior ICI exposure had OSORRs of 11.5% in the liver, 11.4% in the lung, 27.8% in LNs, and 7.4% in other metastatic sites (132 individual lesions). Furthermore, patients who achieved a response in the liver or the lung had longer progression-free and overall survival, compared with those without responses. Nivo monotherapy yielded OSORRs of 13.5%, 25.3%, 39.3%, and 18.4% in the liver, lungs, LNs, and other metastatic sites, respectively.
Nivo/Ipi combination therapy induced superior intrahepatic responses compared to Nivo monotherapy in patients with advanced HCC without prior ICI exposure, highlighting its potential to overcome liver-specific immune tolerance.
免疫检查点抑制剂（ICI）单药治疗在晚期肝细胞癌（HCC）患者中引起的肝内反应有限。在此，我们研究了纳武单抗联合伊匹单抗（Nivo/Ipi）与纳武单抗（Nivo）单药治疗相比，考虑既往ICI暴露情况的器官特异性客观缓解率（OSORR）。
我们分析了韩国五个转诊癌症中心接受Nivo/Ipi治疗的患者的204个病灶和接受Nivo治疗的晚期HCC患者的305个病灶。根据实体瘤疗效评价标准1.1，采用器官特异性反应标准，依据指定部位：肝脏、肺、淋巴结（LNs）和其他转移部位。
Nivo/Ipi联合治疗在肝脏、肺、LNs和其他转移部位的OSORR分别为18.1%、17.7%、30.0%和12.5%。既往未接受ICI治疗的患者在肝脏、肺、LNs和其他转移部位的OSORR分别为29.0%、31.3%、33.3%和23.1%（72个个体病灶）。相反，既往接受过ICI治疗的患者在肝脏、肺、LNs和其他转移部位的OSORR分别为11.5%、11.4%、27.8%和7.4%（132个个体病灶）。此外，与无反应者相比，在肝脏或肺中取得反应的患者无进展生存期和总生存期更长。Nivo单药治疗在肝脏、肺、LNs和其他转移部位的OSORR分别为13.5%、25.3%、39.3%和18.4%。
在既往未接受ICI治疗的晚期HCC患者中，Nivo/Ipi联合治疗诱导的肝内反应优于Nivo单药治疗，突出了其克服肝脏特异性免疫耐受的潜力。
