Kim Yoon Jun, Merle Philippe, Finn Richard S, Kudo Masatoshi, Klümpen Heinz-Josef, Lim Ho Yeong, Ikeda Masafumi, Granito Alessandro, Masi Gianluca, Gerolami René, Cho Sung Bum, Hsu Chih-Hung, Huang Yi-Hsiang, Jeng Long-Bin, Kim Do Young, Lin Shi-Ming, Pinter Matthias, Shao Guoliang, Kato Naoya, Kurosaki Masayuki, Numata Kazushi, Kuo Kung-Kai, Mao Yilei, Lin Yih-Jyh, Zhu Kangshun, Twumasi-Ankrah Philip, Khan Javeed, Awan Maria, Ozgurdal Kirhan, Qin Shukui
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Hepatology and Gastroenterology, Groupement Hospitalier Lyon Nord, Hôpital de la Croix-Rousse, Lyon, France.
Liver Cancer. 2024 Dec 18;14(4):391-407. doi: 10.1159/000542285. eCollection 2025 Aug.
In the phase 3 RESORCE trial, regorafenib prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC) whose disease progressed on prior sorafenib. The prospective, observational REFINE study aimed to evaluate the safety and effectiveness of regorafenib in a broader population of patients in real-world clinical practice, including patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, Child-Pugh B liver status, and sorafenib intolerance.
This international, prospective, multicenter study (NCT03289273) enrolled patients with uHCC for whom the decision to treat with regorafenib was made by their physician before enrollment, according to the local health authority-approved label. The primary aim was to evaluate the safety of regorafenib, including the incidence of treatment-emergent adverse events (TEAEs) and dose modifications due to TEAEs.
Of the 1,028 patients enrolled, 1,005 initiated regorafenib and were eligible for analysis. Median age was 66 years (range 21-94); most patients were male (83%), Child-Pugh A (61%), and had an ECOG PS of 0 or 1 (82%) at study entry. Overall, 47%, 11%, and 40% of patients initiated regorafenib at 160, 120, and 80 mg/day, respectively. Median treatment duration was 3.7 months (range 1 day to 38.9 months). Dose modifications and permanent discontinuation of regorafenib due to TEAEs occurred in 45% and 31% of patients, respectively. The most common drug-related TEAEs were hand-foot skin reaction (31%), diarrhea (26%), and fatigue (15%). Median OS was 13.2 months (95% confidence interval 11.6, 14.8).
The results of the real-world REFINE study confirmed the safety and effectiveness of regorafenib in a broad population of patients with uHCC. Of patients who received standard regorafenib dosing in REFINE, safety and efficacy findings were consistent with those reported in the RESORCE trial.
在3期RESORCE试验中，瑞戈非尼延长了既往接受索拉非尼治疗后疾病进展的不可切除肝细胞癌（uHCC）患者的总生存期（OS）。前瞻性观察性REFINE研究旨在评估瑞戈非尼在更广泛的真实世界临床实践患者群体中的安全性和有效性，包括东部肿瘤协作组体能状态（ECOG PS）≥2、Child-Pugh B级肝功能以及对索拉非尼不耐受的患者。
这项国际、前瞻性、多中心研究（NCT03289273）纳入了uHCC患者，这些患者在入组前由其医生根据当地卫生当局批准的标签决定接受瑞戈非尼治疗。主要目的是评估瑞戈非尼的安全性，包括治疗中出现的不良事件（TEAE）的发生率以及因TEAE导致的剂量调整。
在1028名入组患者中，1005名开始使用瑞戈非尼并符合分析条件。中位年龄为66岁（范围21 - 94岁）；大多数患者为男性（83%），Child-Pugh A级（61%），研究入组时ECOG PS为0或1（82%）。总体而言，分别有47%、11%和40%的患者开始使用瑞戈非尼的剂量为160、120和80毫克/天。中位治疗持续时间为3.7个月（范围1天至38.9个月）。分别有45%和31%的患者因TEAE对瑞戈非尼进行了剂量调整和永久停药。最常见的与药物相关的TEAE为手足皮肤反应（31%）、腹泻（26%）和疲劳（15%）。中位OS为13.2个月（95%置信区间11.6，14.8）。
真实世界REFINE研究的结果证实了瑞戈非尼在广泛的uHCC患者群体中的安全性和有效性。在REFINE中接受标准瑞戈非尼剂量治疗的患者中，安全性和有效性结果与RESORCE试验中报告的结果一致。
