Lenvima (lenvatinib) - 3 indications

Scroll down for information on each indication:

• the treatment of thyroid cancer; approved February 2015
• the treatment of advanced renal cell carcinoma; approved May 2016
• the treatment of unresectable hepatocellular carcinoma; approved August 2018

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 following:

• the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer
• in combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
• for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)

Lenvima is supplied as capsules for oral administration. Take Lenvima once daily, with or without food, at the same time each day. If a dose is missed and cannot be taken within 12 hours, skip that dose and take the next dose at the usual time of administration. Scroll down for recommended dosing/administration for each indication.

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. 

Side Effects

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

• hypertension
• fatigue
• diarrhea
• arthralgia/myalgia
• decreased appetite
• weight decreased
• nausea
• stomatitis
• headache
• vomiting
• proteinuria
• palmar-plantar erythrodysesthesia syndrome
• abdominal pain
• dysphonia

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

• diarrhea
• fatigue
• arthralgia/myalgia
• decreased appetite
• vomiting
• nausea
• stomatitis/oral inflammation
• hypertension
• peripheral edema
• cough
• abdominal pain
• dyspnea
• rash
• weight decreased
• hemorrhagic events
• proteinuria

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 

Indication 1 - thyroid cancer

approved February 2015

Dosing/Administration

The recommended dosage of Lenvima is 24 mg orally once daily until disease progression or until unacceptable toxicity.

Clinical Trial Results

The FDA approval of Lenvima for thyroid cancer was based on a multicenter, randomized, double-blind, placebo-controlled trial in 392 subjects with locally recurrent or metastatic radioactive iodine-refractory differentiated thyroid cancer and radiographic evidence of disease progression within 12 months prior to randomization, confirmed by independent radiologic review. The subjects received Lenvima 24 mg once daily (n=261) or placebo (n=131) until disease progression. Study results showed Lenvima-treated subjects lived a median of 18.3 months without their disease progressing (progression-free survival), compared to a median of 3.6 months for subjects who received placebo. Additionally, 65% of subjects treated with Lenvima saw a reduction in tumor size, compared to 2% of subjects who received a placebo.

Indication 2 - advanced renal cell carcinoma

approved May 2016

Dosing/Administration

The recommended dosage of Lenvima is 18 mg in combination with 5 mg everolimus orally once daily until disease progression or until unacceptable toxicity. Refer to everolimus prescribing information for recommended everolimus dosing information.

Clinical Trial Results

The FDA approval of Lenvima for renal cell carcinoma was based on a multicenter study which randomized 153 patients with advanced or metastatic renal cell carcinoma who had previously received anti-angiogenic therapy to Lenvima 18 mg plus everolimus 5 mg, Lenvima 24 mg monotherapy, or everolimus 10 mg monotherapy. All medications were administered orally once daily. The primary endpoint was investigator-assessed PFS evaluated according to RECIST 1.1. Lenvima and everolimus (LEN+EVE) resulted in a median PFS nearly three times that of everolimus alone. The median PFS, or the length of time from randomization until disease progression or death, in patients treated with the combination (n=51) was 14.6 months compared with 5.5 months for those treated with everolimus alone (n=50). The combination regimen resulted in a 63% reduction in the risk of disease progression or death compared with everolimus alone. The objective response rate was 37% in patients treated with the combination regimen (35% partial response + 2% complete response) compared to 6% (all partial response) in patients treated with everolimus alone. The patients who received LEN+EVE experienced a 10.1-month increase in median OS compared with those who received everolimus monotherapy (25.5 months) versus 15.4 months. This OS analysis was conducted when 63% of deaths had occurred in the combination arm and 74% of deaths had occurred in the everolimus arm.

Indication 3 - unresectable hepatocellular carcinoma

approved August 2018

Dosing/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 Trial Results

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.