A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)
Akihiko Ichida,
Junichi Arita,
Etsuro Hatano,
Susumu Eguchi,
Akio Saiura,
Hiroaki Nagano,
Junichi Shindoh,
Masaji Hashimoto,
Nobuyuki Takemura,
Kojiro Taura,
Yoshihiro Sakamoto,
Yu Takahashi,
Yasuji Seyama,
Yasuharu Sasaki,
Kohei Uemura,
Norihiro Kokudo,
Kiyoshi Hasegawa
Affiliations
Akihiko Ichida
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Junichi Arita
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Etsuro Hatano
Department of Gastroenterological Surgery, Hyogo Medical University, Kobe, Japan
Susumu Eguchi
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Akio Saiura
Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
Hiroaki Nagano
Department of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
Junichi Shindoh
Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
Masaji Hashimoto
Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
Nobuyuki Takemura
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
Kojiro Taura
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Yoshihiro Sakamoto
Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
Yu Takahashi
Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital for Japanese Foundation for Cancer Research, Tokyo, Japan
Yasuji Seyama
Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
Yasuharu Sasaki
JCRAC Data Center, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
Kohei Uemura
Biostatistics and Bioinformatics Course, The University of Tokyo, Tokyo, Japan
Norihiro Kokudo
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
Kiyoshi Hasegawa
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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.
