Lenvatinib Approved for Refractory Thyroid Cancer

Zosia Chustecka

Disclosures

February 13, 2015

A new treatment option for refractory differentiated thyroid cancer (DTC), which has progressed despite radioactive iodine therapy, has been approved by the US Food and Drug Administration (FDA) today — lenvatinib (Lenvima, Eisai).

Lenvatinib underwent priority review, and was approved 2 months ahead of schedule, in the same week that the pivotal study that forms the basis of approval was published (N Engl J Med. 2015;372:621-630).

This is the second drug approved for this patient population. The other is sorafenib (Nexavar, Bayer), which was approved in November 2013. Both drugs are oral tyrosine kinase inhibitors.

"Options for patients with refractory thyroid cancer have been very limited, but we now have two agents that have shown a clear benefit in large phase 3 studies," commented Stephen Liu, MD, assistant professor of medicine at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, when the results with lenvatinib were first presented.

"These studies highlight our collective ability to conduct large trials for relatively rare cancers," he added.

"The development of new therapies to assist patients with refractory disease is of high importance to the FDA," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Today's approval gives patients and healthcare professionals a new therapy to help slow the progression of DTC."

DTC is the most common type of thyroid cancer, accounting for approximately 95% of all thyroid cancers. Most patients respond to treatment very well, but about 10% go on to develop refractory disease. The National Cancer Institute estimates that 62,980 Americans were diagnosed with thyroid cancer and 1890 died from the disease in 2014.

Approval Based on SELECT Trial

The approval of lenvatinib for DTC was based on the SELECT trial, the results from which, as previously reported by Medscape Medical News, were presented at the 2014 annual meeting of the American Society of Clinical Oncology, and were recently published.

The SELECT trial was conducted in 392 patients with progressive, radioactive-iodine-refractory DTC who were randomly assigned to receive either lenvatinib or placebo. The primary end point of median progression-free survival was 18.3 months with the drug, compared with 3.6 months for placebo (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 - 0.31; P < .001).

Additionally, 65% of patients taking lenvatinib saw a reduction in tumor size, compared with 2% on placebo.

Once the trial was unblinded, a majority of patients who had been randomly assigned to receive the placebo went on to receive treatment with lenvatinib. This high crossover rate is cited by the trialists as the reason for why they do not expect to see a difference in overall survival.

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

The FDA also notes that lenvatinib 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.

Lenvatinib is awaiting approval in Europe and elsewhere in the world, and is also being investigated in company-sponsored trials in liver, kidney, and non-small cell lung cancer.

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