Lenvatinib (Lenvima)

Approved for patients with progressive, differentiated, radio-iodine-refractory thyroid cancer.

Approved for the treatment of patients with advanced or metastatic renal cell carcinoma previously treated with a vascular endothelial growth factor (VEGF) targeted therapy.

Brand name Lenvima.

Approved lenvatinib as a first-line treatment for patients with unresectable hepatocellular carcinoma.

REFLECT trial compared lenvatinib to sorafenib in unresectable hepatocellular carcinoma: lenvatinib had improved progression free survival, time to progression, and overall response rate.

Inhibits multiple kinases that promote cancer cell growth and division.

It acts as a multiple kinase inhibitor. 

A tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor receptors VEGFR1-3.

Acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.


It inhibits the three main vascular endothelial growth factor receptors VEGFR1, 2 and 3, as well as fibroblast growth factor receptors (FGFR) 1, 2, 3 and 4, platelet-derived growth factor receptor (PDGFR) alpha, c-Kit, and the RET proto-oncogene. 



Some of the above proteins play roles in cancerogenic signalling pathways. 

Inhibits fibroblast growth factor receptor.

Pregnancy category AU: D


Routes of administration oral


Bioavailability 85% 


Protein binding 98–99%


Metabolism CYP3A4, aldehyde oxidase, non-enzymatic



Lenvatinib is absorbed quickly from the gut.


It reaches peak blood plasma concentrations after one to four hours.


 It is oxidized by cytochrome P450 enzymes (CYP), and further metabolized to the quinolinones.


Lenvatinib is metabolized by the liver enzyme CYP3A4 to substances called M2′ and M3, the main metabolites in the feces. 


Non-enzymatic metabolization also occurs, resulting in a low potential for interactions with enzyme inhibitors and inducers


Terminal half-life is 28 hours.


Excretion 65% feces, 25% urine

In a randomized trial comparing 24 mg a day of oral lenvatinib versus placebo, the median progression free survival was significantly longer in the lenvatinib group of 18.3 months versus the placebo group of 3.6 months (SELECT study).

In the above study the response rate was significantly higher in the lenvatinib group than in those receiving placebo, 64.8% versus 1.5%, respectively.

In a phase II trial of 153 patients with renal cancer previously treated with VEGF targeted therapy: Patients were randomized to Everiolimus or lenvatinib alone, or a combination of these 2 drugs-the median duration of response was longest inthe drug combination at 13.1 months compared to Levatinib alone at 7-1/2 months and Everiolimus alone at 8.5 months.

In the above study 65% of patients taking lenvatinib saw a reduction in tumor size, compared with 2% on placebo.

Approved for the treatment of differentiated thyroid cancer that is either locally recurrent or metastatic, progressive, and did not respond to treatment with radioactive iodine.


It is approved in combination with everolimus for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy.



The drug is also approved for hepatocellular carcinoma that cannot be removed surgically in patients who have not received cancer therapy by mouth or injection.


Approved lenvatinib for the first-line treatment of people with unresectable hepatocellular carcinoma (HCC).


Approved in  combination of the immunotherapy pembrolizumab (Keytruda) plus the multiple receptor tyrosine kinase inhibitor lenvatinib (Lenvima) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), in patients who have disease progression following prior systemic therapy in any setting; and are not candidates for curative surgery or radiation.

The most common side effects are: Hypertension, diarrhea, fatigue, impaired appetite, weight loss, and nausea.

VEGFR2 inhibition is associated with  hypertension.

Side effects: Hypertension is seen in 73% of patients, followed by diarrhea (67%) and fatigue (67%).


Other common side effects include: decreased appetite, hypotension, thrombocytopenia, nausea, muscle and bone pain.


It  moderately prolongs QT time.


The addition of other drugs that prolong QT interval, could increase the risk of a type of torsades de pointes. 

Other less common side effects but more serious including cardiac failure, arterial thrombotic events, hepatotoxicity and renal insufficiency.

This is the second drug approved for this patient population, and the other is sorafenib.

Differentiated thyroid cancer is the most common type of thyroid cancer, accounting for approximately 95% of all thyroid cancers.

About 10% go on to develop refractory disease.

The pivotal phase 3 KEYNOTE-775/Study 309 trial evaluating the use of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) met its dual primary end points of overall and progression-free survival in patients with advanced endometrial cancer.


Patients had advanced endometrial cancer following at least 1 prior platinum-based regimen.


Positive results were reported in the mismatch repair proficient (pMMR) subgroup and patients whose disease is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).


Pembrolizumab plus lenvatinib demonstrated a statistically significant and clinically meaningful improvement in OS, PFS, and response rate versus chemotherapy treatment of physician’s choice of doxorubicin or paclitaxel in endometrial cancers.


Lenvatinib plus Pembrolizumab  is associated with a significantly longer progressive free survival and overall survival in advanced renal cell carcinoma than sutinib.

PENMMELA regimen consisting of Pembrolizumab and lenvatinib had a response rate of 58% in pleural Mesothelioma.

Most common adverse effects of lenvatinib are hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia.

May cause serious adverse effects, including cardiac failure, arterial thromboembolic events, hepatotoxicity, renal failure and impairment, gastrointestinal perforation or fistula formation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhage, risks to an unborn child if a patient becomes pregnant during treatment, and impairing suppression of the production of thyroid-stimulating hormone.

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