Lenvatinib Approved for Certain Thyroid Cancers

The FDA approved lenvatinib (Lenvima; Eisai), a tyrosine kinase inhibitor (TKI), to treat patients with progressive, differentiated thyroid cancer (DTC) that is refractory to treatment with radioactive iodine (RAI). The approval provides these patients with a second—and potentially more effective—therapeutic option.

The decision was based on findings from the phase III SELECT study, in which lenvatinib extended median progression-free survival (PFS) by 14.7 months compared with placebo in patients with RAI-resistant DTC. The findings, presented last spring at the American Society of Clinical Oncology's annual meeting, were published on February 12, the day before the FDA decision was announced (N Engl J Med 2015;372:621–30).

About 85% of the 60,000 cases of thyroid cancer diagnosed in the United States annually are DTCs. While many patients with DTC can be cured with surgery and RAI, about 10% of them do not respond to standard treatment and develop metastases, often to the liver, lungs, and bones.

“The efficacy of lenvatinib is much better than that of any other drug, and it should be the drug of choice for first-line treatment” of patients with advanced refractory thyroid cancer, says SELECT lead author Martin Schlumberger, MD, of the Institut Gustave Roussy in Villejuif, France.

The only other drug approved for these patients is sorafenib (Nexavar; Bayer and Onyx Pharmaceuticals), a TKI approved in 2013 based on results from the phase III DECISION trial. In that study, patients with RAI-refractory disease showed a 5-month improvement in median PFS compared with placebo (Lancet 2014;384:319–28).

Both drugs inhibit a range of molecular targets thought to be involved in aggressive thyroid cancer, including VEGFR1–3, PDGFR-ß, KIT, and RET. The SELECT study authors speculated that the longer PFS observed in the SELECT trial versus the DECISION trial could be due to the inhibition of unique targets of lenvatinib, including FGFR1–4.

The SELECT trial authors noted that neither BRAF nor RAS mutation status was predictive of response to lenvatinib and that further investigations into biomarkers of efficacy are needed. They also observed that the PFS benefit was maintained across all subgroups.

“Similar benefits were observed in treatment-naïve patients and those who received one other TKI,” says Schlumberger, “demonstrating the absence of cross-resistance.”

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