National Stroke Foundation

Lenvima (lenvatinib)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved August 2018

Specific Treatments:

unresectable hepatocellular carcinoma

General Information

Lenvima (lenvatinib) is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4).

Lenvima is specifically indicated for the first-line treatment of patients with unresectable hepatocellular carcinoma.

Lenvima is supplied as a capsule for oral administration. The recommended dosage of Lenvima for HCC is based on actual body weight:

• 12 mg for patients greater than or equal to 60 kg or

• 8 mg for patients less than 60 kg

Take Lenvima orally once daily until disease progression or until unacceptable toxicity.  

Clinical Results

FDA Approval

The FDA approval of Lenvima for hepatocellular carcinoma was based on REFLECT, a randomized, multicenter, open-label trial to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients (N=954) with unresectable hepatocellular carcinoma (HCC). Patients at 154 trial sites in 20 countries were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival, tested first for non-inferiority to sorafenib, then for superiority. Patients randomized to the Lenvima arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. Lenvima achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with Lenvima experienced a median OS of 13.6 months compared to 12.3 months with sorafenib. In addition, Lenvima showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of progression-free survival (PFS) and objective response rate (ORR) when compared with sorafenib.

Side Effects

Adverse effects associated with the use of Lenvima for HCC may include, but are not limited to, the following:

hypertension

fatigue

diarrhea

decreased appetite

arthralgia/myalgia

decreased weight

abdominal pain

palmar-plantar erythrodysesthesia syndrome

proteinuria

dysphonia

hemorrhagic events

hypothyroidism

nausea 

Mechanism of Action

Lenvima (lenvatinib) is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. 

Additional Information

For additional information regarding Lenvima or hepatocellular carcinoma, please visit http://www.lenvima.com/inoperable-liver-cancer