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J Gastroenterol. 2017 Apr;52(4):512-519. doi: 10.1007/s00535-016-1263-4. Epub 2016 Oct 4.

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma.

Author information

1
Department of Hepatology, Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo, 105-8470, Japan. ikedakenji@tora.email.ne.jp.
2
Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.
3
Department of Hepatobiliary and Pancreatology, Saga-Ken Medical Centre KOSEIKAN, Saga, Japan.
4
Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
5
Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
6
Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
7
Eisai Co., Ltd.,, Tokyo, Japan.
8
Shunan Memorial Hospital, Yamaguchi, Japan.
9
Department of Hepatology, Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo, 105-8470, Japan.

Abstract

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.

KEYWORDS:

E7080; Hepatocellular carcinoma; Lenvatinib; Tyrosine kinase inhibitor; Vascular endothelial growth factor inhibitor

PMID:
27704266
PMCID:
PMC5357473
DOI:
10.1007/s00535-016-1263-4
[Indexed for MEDLINE]
Free PMC Article

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