Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma
Kenji Ikeda1, Masatoshi Kudo2, Seiji Kawazoe3
1Department of Hepatology, Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo, 105-8470, Japan. ikedakenji@tora.email.ne.jp.
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.
Insights
Lenvatinib demonstrated clinical activity in advanced hepatocellular carcinoma (HCC), with a median time to progression of 7.4 months. Early dose modification based on body weight is recommended for lenvatinib in HCC treatment.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor.
- It targets VEGFR, FGFR, PDGFRα, RET, and KIT.
- This study investigated lenvatinib in advanced hepatocellular carcinoma (HCC).
Purpose of the Study:
- To evaluate the efficacy and safety of lenvatinib in patients with advanced HCC.
- To determine time to progression (TTP) as the primary endpoint.
- To assess objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
Main Methods:
- A phase 2, single-arm, open-label, multicenter study.
- 46 patients with advanced HCC received lenvatinib 12 mg once daily.
- Efficacy assessed by TTP, ORR, DCR, OS; safety by adverse events (AEs).
Main Results:
- Median TTP was 7.4 months; ORR was 37%, DCR was 78%.
- Median OS was 18.7 months.
- Common AEs included hypertension (76%), palmar-plantar erythrodysesthesia (65%), decreased appetite (61%), and proteinuria (61%). 74% required dose modification.
Conclusions:
- Lenvatinib 12 mg QD showed clinical activity and acceptable toxicity in advanced HCC.
- Early dose modification was necessary for patients with lower body weight.
- Future lenvatinib development in HCC should consider body weight-based dose adjustments.
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