Introduction The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

中文翻译：

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一项评估术前乐伐替尼治疗晚期肝细胞癌患者疗效和安全性的多中心 2 期试验（LENS-HCC 试验）。


简介 III 期 REFLECT 试验表明，乐伐替尼在不可切除的肝细胞癌 (HCC) 患者的无进展生存期 (PFS)、进展时间和客观缓解率 (ORR) 方面优于索拉非尼。本研究评估了术前乐伐替尼治疗对于肿瘤学或技术上不可切除的 HCC 患者的疗效和安全性。方法 在这项多中心单组 II 期试验中，纳入了患有晚期 HCC 和提示不良预后因素（宏观血管侵犯、肝外转移或多结节性肿瘤）的患者。具有这些因素的患者，即使是技术上可切除的 HCC，也被定义为肿瘤学上不可切除的患者，因为预计术后预后不良。乐伐替尼治疗8周后，评估患者的可切除性，如果技术上认为肿瘤可切除，则进行肿瘤切除。主要终点是手术切除率。次要终点是宏观治愈性切除率、总生存期 (OS)、ORR、PFS 以及乐伐替尼治疗前后测量的 15 分钟吲哚菁绿保留率的变化。该试验已在日本临床试验登记处注册（s031190057）。结果 2019 年 7 月至 2021 年 1 月期间，来自 11 个中心的 49 名患者（42 名肿瘤学上无法切除的患者和 7 名技术上无法切除的患者）入组。基于 mRECIST 的 ORR 为 37.5%，基于 RECIST 1.1 版的 ORR 为 12.5%。 33例患者接受了手术（手术切除率：67.3%），无围手术期死亡。肿瘤学上无法切除的患者的手术切除率为 76.2%，技术上无法切除的患者的手术切除率为 14.3%。 1 年 OS 率和中位 PFS 分别为 75.9% 和 7.2 个月，中位随访时间为 9.3 个月。结论 本研究中相对较高的手术切除率表明，对于肿瘤学或技术上无法切除的 HCC 患者，乐伐替尼治疗随后进行手术切除是安全和可行的。