{"title":"瑞非尼在一线免疫检查点抑制剂失效后对晚期肝癌患者的疗效：一项多中心研究","authors":"Yuan Cheng, Jun-Ying Wang, You Lu, Yong-Xiang Xia, Hui Zhao, Qi Wang, Xiao-Li Zhu, Qing-Quan Zu, Hui-Kai Li, Zhong Chen, Xiang-Cheng Li","doi":"10.1016/j.hbpd.2025.09.004","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a significant global health challenge. While first-line treatments with immune checkpoint inhibitors (ICIs) have improved patient outcomes, the selection of effective second-line therapies remains unclear. This study evaluated the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based therapies.</p><p><strong>Methods: </strong>Advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies, alone or combined with ICIs were enrolled. Clinical data were collected, and propensity score matching (PSM) was used to ensure comparability between treatment groups. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. The study was registered at www.chictr.org.cn (ChiCTR2400091318).</p><p><strong>Results: </strong>A total of 149 patients were included: 113 in the combination therapy group (Rego-ICI group) and 36 in the regorafenib monotherapy group (Rego group). After PSM, the Rego-ICI group showed significantly improved and OS [19.0 vs. 11.0 months, hazard ratio (HR) = 0.426, 95% confidence interval (CI): 0.235-0.772, P = 0.005] and PFS (4.0 vs. 3.0 months, HR = 0.539, 95% CI: 0.337-0.863, P = 0.010) compared to the Rego group. Differences in ORR and DCR were not statistically significant (ORR: 19.4% vs. 9.7%, P = 0.226; DCR: 64.2% vs. 48.4%, P = 0.139), but the Rego-ICI group showed better disease control. Regorafenib plus ICI improved both OS and PFS with no new safety signals.</p><p><strong>Conclusions: </strong>The combination of ICIs and regorafenib significantly enhances OS in advanced HCC patients post-progression on first-line ICI treatments. These findings support the potential of regorafenib plus ICIs as an effective second-line therapy.</p>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":" ","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy of regorafenib following first-line immune checkpoint inhibitor failure in patients with advanced hepatocellular carcinoma: A multicenter study.\",\"authors\":\"Yuan Cheng, Jun-Ying Wang, You Lu, Yong-Xiang Xia, Hui Zhao, Qi Wang, Xiao-Li Zhu, Qing-Quan Zu, Hui-Kai Li, Zhong Chen, Xiang-Cheng Li\",\"doi\":\"10.1016/j.hbpd.2025.09.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a significant global health challenge. While first-line treatments with immune checkpoint inhibitors (ICIs) have improved patient outcomes, the selection of effective second-line therapies remains unclear. This study evaluated the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based therapies.</p><p><strong>Methods: </strong>Advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies, alone or combined with ICIs were enrolled. Clinical data were collected, and propensity score matching (PSM) was used to ensure comparability between treatment groups. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. The study was registered at www.chictr.org.cn (ChiCTR2400091318).</p><p><strong>Results: </strong>A total of 149 patients were included: 113 in the combination therapy group (Rego-ICI group) and 36 in the regorafenib monotherapy group (Rego group). After PSM, the Rego-ICI group showed significantly improved and OS [19.0 vs. 11.0 months, hazard ratio (HR) = 0.426, 95% confidence interval (CI): 0.235-0.772, P = 0.005] and PFS (4.0 vs. 3.0 months, HR = 0.539, 95% CI: 0.337-0.863, P = 0.010) compared to the Rego group. Differences in ORR and DCR were not statistically significant (ORR: 19.4% vs. 9.7%, P = 0.226; DCR: 64.2% vs. 48.4%, P = 0.139), but the Rego-ICI group showed better disease control. Regorafenib plus ICI improved both OS and PFS with no new safety signals.</p><p><strong>Conclusions: </strong>The combination of ICIs and regorafenib significantly enhances OS in advanced HCC patients post-progression on first-line ICI treatments. 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引用次数: 0
摘要
背景：肝细胞癌（HCC）仍然是一个重大的全球健康挑战。虽然使用免疫检查点抑制剂（ICIs）的一线治疗改善了患者的预后，但选择有效的二线治疗仍不清楚。本研究评估了regorafenib作为晚期HCC患者在ci基础治疗进展后的二线选择的有效性和安全性。方法：纳入来自中国8家医院的晚期HCC患者，这些患者在一线ICI治疗进展后接受瑞非尼治疗，单独或联合ICI治疗。收集临床资料，采用倾向评分匹配（PSM）确保治疗组间的可比性。主要终点是总生存期（OS）。次要终点为无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和治疗相关不良事件。该研究已在www.chictr.org.cn注册（ChiCTR2400091318）。结果：共纳入149例患者：联合治疗组113例（雷戈- ici组），瑞非尼单药治疗组36例（雷戈组）。PSM后，Rego- ici组与Rego组相比，OS (19.0 vs. 11.0个月，风险比（HR) = 0.426, 95%可信区间（CI）： 0.235 ~ 0.772, P = 0.005）和PFS （4.0 vs. 3.0个月，HR = 0.539, 95% CI: 0.337 ~ 0.863, P = 0.010）明显改善。ORR与DCR差异无统计学意义（ORR: 19.4% vs. 9.7%, P = 0.226; DCR: 64.2% vs. 48.4%, P = 0.139），但Rego-ICI组疾病控制较好。Regorafenib + ICI改善了OS和PFS，没有新的安全信号。结论：ICI联合瑞非尼可显著提高一线ICI治疗进展的晚期HCC患者的OS。这些发现支持瑞非尼加ICIs作为有效二线治疗的潜力。
Efficacy of regorafenib following first-line immune checkpoint inhibitor failure in patients with advanced hepatocellular carcinoma: A multicenter study.
Background: Hepatocellular carcinoma (HCC) remains a significant global health challenge. While first-line treatments with immune checkpoint inhibitors (ICIs) have improved patient outcomes, the selection of effective second-line therapies remains unclear. This study evaluated the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based therapies.
Methods: Advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies, alone or combined with ICIs were enrolled. Clinical data were collected, and propensity score matching (PSM) was used to ensure comparability between treatment groups. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. The study was registered at www.chictr.org.cn (ChiCTR2400091318).
Results: A total of 149 patients were included: 113 in the combination therapy group (Rego-ICI group) and 36 in the regorafenib monotherapy group (Rego group). After PSM, the Rego-ICI group showed significantly improved and OS [19.0 vs. 11.0 months, hazard ratio (HR) = 0.426, 95% confidence interval (CI): 0.235-0.772, P = 0.005] and PFS (4.0 vs. 3.0 months, HR = 0.539, 95% CI: 0.337-0.863, P = 0.010) compared to the Rego group. Differences in ORR and DCR were not statistically significant (ORR: 19.4% vs. 9.7%, P = 0.226; DCR: 64.2% vs. 48.4%, P = 0.139), but the Rego-ICI group showed better disease control. Regorafenib plus ICI improved both OS and PFS with no new safety signals.
Conclusions: The combination of ICIs and regorafenib significantly enhances OS in advanced HCC patients post-progression on first-line ICI treatments. These findings support the potential of regorafenib plus ICIs as an effective second-line therapy.
期刊介绍：
Hepatobiliary & Pancreatic Diseases International (HBPD INT) (ISSN 1499-3872 / CN 33-1391/R) a bimonthly journal published by First Affiliated Hospital, Zhejiang University School of Medicine, China. It publishes peer-reviewed original papers, reviews and editorials concerned with clinical practice and research in the fields of hepatobiliary and pancreatic diseases. Papers cover the medical, surgical, radiological, pathological, biochemical, physiological and historical aspects of the subject areas under the headings Liver, Biliary, Pancreas, Transplantation, Research, Special Reports, Editorials, Review Articles, Brief Communications, Clinical Summary, Clinical Images and Case Reports. It also deals with the basic sciences and experimental work. The journal is abstracted and indexed in SCI-E, IM/MEDLINE, EMBASE/EM, CA, Scopus, ScienceDirect, etc.
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