A Multicenter Retrospective Study: Impact of First-Line Treatment Strategies on second-Line Efficacy and Safety of Regorafenib with or Without PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma

作者：Weihong Ma, Yinyin Li, Yinying Lu, Zhipeng Liang, Hongli Yu, Jie Han, Jiaqi Liu, Wenjing Wang, Caiyun Peng, Jiamin Cheng · 发表于：Journal of Hepatocellular Carcinoma · 年份：2025 · DOI：10.2147/jhc.s456712 · 被引用次数：8 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Cholangiocarcinoma and Gallbladder Cancer Studies

Purpose: Amid the era of targeted-immunotherapy for hepatocellular carcinoma (HCC), the selection of second-line therapy following failure of diverse first-line regimens remains inadequately explored. This multicenter study aimed to assess how first-line treatment strategies impact the efficacy and safety of second-line regorafenib-either alone or in combination with PD-1 inhibitors-in patients with unresectable HCC (uHCC). Specifically, we focused on two key populations: patients who failed first-line tyrosine kinase inhibitor (TKI) monotherapy, and a rapidly expanding cohort who progressed after first-line TKI plus PD-1 inhibitor combination therapy, and to address the critical clinical dilemma of whether to continue immunotherapy in the second line. Patients and Methods: This retrospective study enrolled 288 uHCC patients from five centers, stratified into two cohorts based on first-line therapy: 126 patients with first-line TKI monotherapy (Pre-Monotherapy cohort) and 162 with first-line TKI+PD-1 combination therapy (Pre-Combination cohort). All received second-line regorafenib alone or with PD-1 inhibitors. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included progression-free survival (PFS),objective response rate (ORR), disease control rate (DCR), and safety. Results: In the Pre-Monotherapy cohort, regorafenib plus PD-1 significantly improved outcomes versus regorafenib alone: mPFS (10.5 vs 4.7 months, p<0.001), ...