Results from the SELECT Phase III study (Study of (E7080) LEnvatinib in differentiated Cancer of the Tgyroid) presented at the 50th Annual Meeting of the American Society of Clinical Oncology(ASCO), being held May 30 – June 3, 2014 in Chicago, Ill, show that lenvatinib (Eisai Co., Ltd.), an investigational selective tyrosine kinase inhibitor (TKI) with a novel binding mode, the first-in-class of its kind, is highly effective against differentiated thyroid cancer that is resistant to 
standard radioiodine (RAI) therapy (RR-DTC).[1][2]
The new oral targeted drug delayed disease progression by 14.7 months, and nearly two thirds of patients experienced tumor shrinkage. The median overall survival (OS) has not yet been reached.
?We are confident that, based on our findings, lenvatinib will eventually become a standard treatment for radioiodine-resistant thyroid cancer,? said lead study author Martin Schlumberger, MD, a professor of oncology at theUniversit? Paris-Sud, Paris, France. ?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.?
…lenvatinib, offers an effective option with reasonable side effects and can help patients live longer before the disease worsens…
Thyroid cancer refers to cancer that forms in the tissues of the thyroid gland, located at the base of the throat near the trachea. It is the most common endocrine malignancy and global figures show that its incidence has significantly increased over the last 50 years. The disease is more common in women than in men and usually occurs between the ages of 25 and 65.
The most common types of thyroid cancer, papillary and follicular (including H?rthle cell), are classified as differentiated thyroid cancer and account for approximately 95% of all cases (In the United States it is estimated that the disease accounts for about 85% of the 60,000 thyroid cancer cases diagnosed each year). The remaining cases are classified as either undifferentiated(3-5% of cases) and medullary carcinoma (1-2% of cases).
While most differentiated thyroid cancer patients are curable with standard treatment – surgery and radioactive iodine treatment or RAI, a small percentage of patients, between 5 – 15%, develop RAI resistance and do not respond to therapy. There are limited treatment options for this difficult-to-treat, life-threatening and treatment-refractory form of thyroid cancer. This type of the disease has a significant unmet treatment need.
Investigational drug
Lenvatinib is an oral tyrosine kinase inhibitor or TKI that blocks several targets in a cancer cell, including VEGFR1-3, FGFR 1-4, PDGFR-?, KIT, and RET. It is 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 this study, 392 patients with advanced, RAI-resistant, differentiated thyroid cancer that had progressed within a 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.
Statistically significant improvement
Approximately 65% of patients experienced tumor shrinkage in the lenvatinib arm, compared to only 3% in the placebo arm. The majority of responses occurred within two months of starting treatment. The median progression-free survival was 18.3 months in the lenvatinib arm vs. 3.6 months in the placebo arm. The median overall survival has not been reached.
The five most common side effects of lenvatinib were high blood pressure, diarrhea, decreased appetite, decreased weight, and nausea. Although the side effects necessitated dose reductions in 78.5% of patients, the benefit of lenvatinib persisted with decreased dose, Schlumberger noted.
Living longer
?The progress we?re seeing with targeted agents for uncommon cancers is encouraging, noted Gregory A. Masters, MD, ASCO Expert working at theHelen F. Graham Cancer Centerin Newark, Delaware. ?Patients with differentiated thyroid cancer have historically had limited options when the disease progresses despite radioactive iodine therapy. Now this new drug, lenvatinib, offers an effective option with reasonable side effects and can help patients live longer before the disease worsens.?
For more information:
[1] Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). 2014 ASCO Annual Meeting, Oral Abstract Session, Monday June 2, 8:00 AM to 11:00 AM. Abstract No: LBA6008, Citation: J Clin Oncol 32:5s, 2014 (suppl; abstr LBA6008)[Abstract]
[2] NCT01321554 – A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer [Study Record Detail]
Photo: Martin Schlumberger M.D., speaks at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO). Photo Courtesy: ?ASCO/Phil McCarten.
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