ASCO 2014: Lenvatinib Yields High Response Rates, Delays Progression in Patients With Radioiodine-Resistant Differentiated Thyroid Cancer


Key Points

  • Lenvatinib delayed disease progression by 14.7 months compared to placebo in a phase III study of patients with radioiodine–refractory differentiated thyroid cancer.
  • Patients receiving lenvatinib had a high objective response rate of 65%, with time to response of only 2 months.
  • Almost all patients experienced treatment-related adverse events leading to dose reduction in 68% of patients and discontinuation of treatment in 14%.

A phase III, multicenter, double-blind, placebo-controlled study found that the oral targeted drug lenvatinib is highly effective among patients with differentiated thyroid cancer resistant to standard radioiodine therapy. “The main result is an extraordinary improvement in progression-free survival from 3.6 months in the placebo arm to 18.3 months in the lenvatinib arm, so the benefit is more than 14 months,” lead study author Martin Schlumberger, MD, Professor of Oncology at the University Paris Sud in Paris, reported at the 2014 ASCO Annual Meeting press briefing on targeted therapies (Abstract LBA6008).

“Furthermore, we had a high objective response rate of 65%,” Dr. Schlumberger said. This included complete responses in four patients receiving lenvatinib. In comparison, the objective response rate in the placebo group was only 2%. “Interestingly, the time to objective response [for lenvatinib] was only 2 months,” he said. Median overall survival has not yet been reached.

Agent Blocks Several Targets

Lenvatinib is an oral tyrosine kinase inhibitor that blocks several targets, including VEGFR1-3, FGFR 1-4, PDGFRβ, KIT, and RET. It is currently being explored in phase II and phase III clinical trials as a potential treatment for liver, lung, and kidney cancers and other types of solid tumors.

In the SELECT (Study of [E7080] Lenvatinib in Differentiated Cancer of the Thyroid) trial, 392 patients with advanced, radioactive iodine–resistant, differentiated thyroid cancer that had progressed within 1 year were randomly assigned to treatment with either lenvatinib or placebo. Patients on the placebo arm were allowed to cross over to the lenvatinib arm upon disease progression. The median age of patients was 63 years and 51% were male.

Adverse Events Led to Dose Reductions

“Treatment-emergent adverse events appeared in almost all patients” receiving lenvatinib, Dr. Schlumberger noted. The most common were hypertension (68%), diarrhea (60%), fatigue/asthenia (59%), decreased appetite (50%), and nausea/vomiting (46%).

Treatment-related adverse events led to dose reduction in 68% of patients and to discontinuation of treatment in 14% of patients. “Fatal events [not related to progressive disease] occurred in 20 patients … and these were assessed to be treatment-related by investigators in six patients,” Dr. Schlumberger stated. Overall, there were 71 deaths in the lenvatinib group (27.2%) and 47 deaths in the placebo group (35.9%).

Historically Limited Options

Although differentiated thyroid cancer is generally curable with standard treatment, surgery and radioactive iodine, 5% to 15% of patients develop radioactive iodine resistance. Another targeted drug, sorafenib (Nexavar), was approved by the U.S. Food and Drug Administration in November 2013 to treat metastatic differentiated thyroid cancer.

“Patients with differentiated thyroid cancer have historically had limited options when the disease progresses despite radioactive iodine therapy,” said press briefing moderator Gregory A. Masters, MD, Director, Medical Oncology Fellowship, and Attending Physician, Helen F. Graham Cancer Center, Newark, Delaware.

In response to a reporter’s question about the relative merits of lenvatinib and sorafenib, Dr. Masters replied, “The numbers from the trial presented today certainly show a higher response rate and a longer prolongation of progression-free survival than the sorafenib study presented last year, but at the same time, we really couldn’t make a direct comparison without doing that randomized trial. Certainly that is something that would need to be considered in order to determine which was the most effective and safest therapy, because there always is that trade-off.”

“We are confident that, based on our findings, lenvatinib will eventually become a standard treatment for radioiodine-resistant thyroid cancer,” Dr. Schlumberger stated. “As little as a year ago, this group of patients had no effective treatment options. It’s remarkable that we now have two active drugs in this setting, both of them tyrosine kinase inhibitors.”

This research was supported by Eisai Inc. Dr. Schlumberger reported a consultant or advisory role with Genzyme/Sanofi, Bayer, Eisai, and AstraZeneca; honoraria from Genzyme/Sanofi, SOBI, Bayer, Eisai, and AstraZeneca; and research funding from Genzyme/Sanofi, Bayer, Eisai, and AstraZeneca. For full disclosures of the study authors, view the study abstract at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.