Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.