FDA Approves Lenvatinib for Differentiated Thyroid Cancer Refractory to Iodine-131

The treatment with lenvatinib improves progression-free survival and response rate

On 13 February, 2015 the US Food and Drug Administration (FDA) granted approval to lenvatinib (Lenvima) to treat patients with progressive, differentiated thyroid cancer whose disease progressed despite receiving radioactive iodine therapy.

It is a most common type of thyroid cancer. The approval is based on results from a global randomised phase III study, published on 12 February 2015 in the New England Journal of Medicine. It offers a new treatment paradigm for a group of patients with radioactive iodine refractory disease for whom until recently, there has been no new effective treatment since the 1940s.

Lenvatinib is an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor alpha, RET, and KIT.

Lenvatinib was reviewed under the FDA’s priority review programme, which provides for an expedited review of drugs that, if approved, would provide significant improvement in safety or effectiveness in the treatment of a serious condition. The drug also received orphan product designation because it is intended to treat a rare disease.

Lenvatinib is being approved approximately two months ahead of the prescription drug user fee goal date of 14 April, 2015, the date when the agency was scheduled to complete its review of the application.

Lenvatinib’s efficacy was demonstrated in 392 participants with progressive, radioactive iodine-refractory differentiated thyroid cancer who were randomly assigned to receive either lenvatinib or a placebo.  Study results showed lenvatinib-treated participants had median of 18.3 months progression-free survival, compared to a median of 3.6 months for participants who received a placebo. Additionally, 65% of participants treated with lenvatinib achieved response seen as a reduction in tumour size, compared to the 2% of participants who received the placebo. A majority of participants randomly assigned to receive the placebo were treated with lenvatinib upon disease progression.

The most common side effects of lenvatinib were hypertension, fatigue, diarrhoea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain and dysphonia.

Lenvatinib may cause serious side effects, including cardiac failure, arterial thromboembolic events, hepatotoxicity, renal failure and impairment, gastrointestinal perforation or fistula formation, QT interval prolongation, hypocalcaemia, reversible posterior leukoencephalopathy syndrome characterised by simultaneous occurrence of headache, confusion, seizures and visual changes, hemorrhage, risks to an unborn child if a patient becomes pregnant during treatment, and impairing suppression of the production of thyroid-stimulating hormone.

Lenvima is marketed by Woodcliff Lake, New Jersey-based Eisai Inc.