Journal Article

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma

Osaki, Yukio, Hayato, Seiichi, Kudo, Masatoshi, Suzuki, Takuya, Kumada, Hiromitsu, Okita, Kiwamu, Ikeda, Masafumi, Ikeda, Kenji, Okusaka, Takuji, Hisai, Takashi, Kawazoe, Seiji, Tamai, Toshiyuki

2017

Overview

Background Lenvatinib is an oral inhibitor of vascular endothelial growth factor receptor 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor alpha, RET, and KIT. This phase 2, single-arm, open-label multicenter study evaluated lenvatinib in advanced hepatocellular carcinoma (HCC). Methods Patients with histologically/clinically confirmed advanced HCC who did not qualify for surgical resection or local therapies received lenvatinib at a dosage of 12 mg once daily (QD) in 28-day cycles. The primary efficacy endpoint was time to progression (TTP) per modified Response Evaluation Criteria in Solid Tumors v1.1; secondary efficacy endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results Between July 2010 and June 2011, 46 patients received lenvatinib at sites across Japan and Korea. The median TTP, as determined by independent radiological review, was 7.4 months [95 % confidence interval (CI): 5.5–9.4]. Seventeen patients (37 %) had partial response and 19 patients (41 %) had stable disease (ORR: 37 %; DCR: 78 %). Median OS was 18.7 months (95 % CI: 12.7–25.1). The most common any-grade adverse events (AEs) were hypertension (76 %), palmar-plantar erythrodysesthesia syndrome (65 %), decreased appetite (61 %), and proteinuria (61 %). Dose reductions and discontinuations due to AEs occurred in 34 (74 %) and 10 patients (22 %), respectively. Median body weight was lower in patients with an early (<30 days) dose withdrawal or reduction than in those without. Conclusions Lenvatinib 12-mg QD showed clinical activity and acceptable toxicity profiles in patients with advanced HCC, but early dose modification was necessary in patients with lower body weight. Further development of lenvatinib in HCC should consider dose modification by body weight. Trial registration ID www.ClinicalTrials.gov NCT00946153.

• Publisher: Springer Japan,Springer,Springer Nature B.V
• Subject: Abdominal Surgery / Adult / Aged / Aged, 80 and over / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - adverse effects / Antineoplastic Agents - therapeutic use / Biliary Tract / Body Weight / Carcinoma, Hepatocellular - diagnostic imaging / Carcinoma, Hepatocellular - drug therapy / Carcinoma, Hepatocellular - pathology / Care and treatment / Colorectal Surgery / Disease Progression / Drug Administration Schedule / Female / Gastroenterology / Growth factors / Hepatology / Hepatoma / Humans / Hypertension / Kaplan-Meier Estimate / Liver Neoplasms - diagnostic imaging / Liver Neoplasms - drug therapy / Liver Neoplasms - pathology / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Middle Aged / Neoplasm Staging / Original Article—Liver / Original —Liver, Pancreas, and Biliary Tract / Pancreas / Phenylurea Compounds - administration & dosage / Phenylurea Compounds - adverse effects / Phenylurea Compounds - therapeutic use / Protein Kinase Inhibitors - administration & dosage / Protein Kinase Inhibitors - adverse effects / Protein Kinase Inhibitors - therapeutic use / Quinolines - administration & dosage / Quinolines - adverse effects / Quinolines - therapeutic use / Surgical Oncology / Tomography, X-Ray Computed / Vascular endothelial growth factor / Young Adult