Based on the phase III SELECT study, lenvatinib looks encouraging against differentiated thyroid cancer that resists standard radioiodine therapy. Sixty-five percent of patients experienced tumor shrinkage, and progression-free survival was extended by 14.7 months.

Based on findings of the phase III SELECT study, lenvatinib (Eisai) looks encouraging for patients with advanced differentiated thyroid cancer that resists standard radioiodine (RAI) therapy. The results were reported by Martin Schlumberger, MD, professor of oncology at the University Paris-Sud in France, during the American Society of Clinical Oncology's Annual Meeting in Chicago, IL, May 30–June 3.

“We have seen extraordinary improvement in progression-free survival for this patient population,” Schlumberger said, noting that no effective therapies even existed a year ago.

The differentiated subtype accounts for about 85% of the approximately 60,000 thyroid cancer cases diagnosed in the United States each year. It is usually curable with surgery and RAI. However, about 10% of patients become RAI-resistant and their disease metastasizes, typically to the liver, lungs, and bones. There is currently one treatment available: sorafenib (Nexavar; Bayer and Onyx Pharmaceuticals), approved by the FDA in November 2013.

Like sorafenib, lenvatinib is a tyrosine kinase inhibitor. It blocks a range of molecular targets, from VEGFR1–3 and FGFR1–4 to PDGFR-β, KIT, and RET. Lenvatinib is being investigated in several types of solid tumors, including liver and kidney cancers, but has yet to be approved.

In the SELECT study, 392 patients with RAI-resistant, differentiated thyroid cancer randomly received either lenvatinib or placebo. Within about 2 months of starting treatment, 65% of patients taking lenvatinib had a complete or partial response, compared with 2% of those taking placebo. Lenvatinib also extended median progression-free survival (PFS) by 14.7 months.

“I was surprised at the large PFS benefit,” said Lori Wirth, MD, medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston and a SELECT U.S. investigator. “Additionally, the response rate with lenvatinib's phase II trial was already 50%; when a drug moves on to phase III, we often see this rate drop rather than increase.”

While differentiated thyroid cancer's molecular drivers are still unclear, Wirth said that “it's hard to argue for focused targeting of single abnormalities when a drug like lenvatinib, which goes after several different kinases, has activity as good as we've seen in SELECT.”

The median overall survival has not been reached in either arm of SELECT, but its design may make this difficult to determine: When disease progression occurred—confirmed by independent radiology review—participants in the placebo arm were given the option to cross over to the lenvatinib arm. “So in theory, most of SELECT's patients could have received lenvatinib at some point, which may obscure an overall survival benefit,” explained Wirth.

Eisai now plans to seek approval for lenvatinib in Japan, the United States, and Europe. “I think choosing between two drugs in our treatment arsenal [sorafenib and lenvatinib] will be a good problem to have,” added Wirth.