Ichida Akihiko, Arita Junichi, Hatano Etsuro, Eguchi Susumu, Saiura Akio, Nagano Hiroaki, Shindoh Junichi, Hashimoto Masaji, Takemura Nobuyuki, Taura Kojiro, Sakamoto Yoshihiro, Takahashi Yu, Seyama Yasuji, Sasaki Yasuharu, Uemura Kohei, Kokudo Norihiro, Hasegawa Kiyoshi
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Gastroenterological Surgery, Hyogo Medical University, Kobe, Japan.
Liver Cancer. 2023 Nov 28;13(3):322-334. doi: 10.1159/000535514. eCollection 2024 Jun.
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.
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).
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.
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.
III期REFLECT试验表明，对于不可切除的肝细胞癌（HCC）患者，乐伐替尼在无进展生存期（PFS）、疾病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肿瘤学上或技术上不可切除的HCC患者的疗效和安全性。
在这项多中心单臂II期试验中，纳入了晚期HCC且具有预后不良因素（肉眼可见血管侵犯、肝外转移或多结节肿瘤）的患者。有这些因素的患者，即使技术上可切除HCC，由于手术后预期预后不良，也被定义为肿瘤学上不可切除。乐伐替尼治疗8周后，评估患者的可切除性，如果肿瘤被认为技术上可切除，则进行肿瘤切除。主要终点是手术切除率。次要终点是肉眼根治性切除率、总生存期（OS）、ORR、PFS以及乐伐替尼治疗前后测量的15分钟时吲哚菁绿潴留率的变化。该试验已在日本临床试验注册中心注册（s031190057）。
2019年7月至2021年1月，来自11个中心的49例患者（42例肿瘤学上不可切除的患者和7例技术上不可切除的患者）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。肿瘤学上不可切除的患者手术切除率为76.2%，技术上不可切除的患者手术切除率为14.3%。1年OS率和中位PFS分别为75.9%和7.2个月，中位随访期为9.3个月。
本研究中观察到相对较高的手术切除率，表明乐伐替尼治疗后手术切除对于肿瘤学上或技术上不可切除的HCC患者具有安全性和可行性。
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