Lenvatinib Phase III Results Show Significant Improvement in Progression-Free Survival in People with Radioiodine-Refractory

Lenvatinib Phase III Results Show Significant Improvement in Progression-Free  Survival in People with Radioiodine-Refractory Differentiated Thyroid Cancer    PR Newswire    HATFIELD, England, May 31, 2014  HATFIELD, England, May 31, 2014 /PRNewswire/ --  Pivotal phase III data for lenvatinib to be presented in a Head and Neck Cancer oral session at  American Society of Clinical Oncology congress ( ASCO)   Eisai announces today pivotal results from the Phase III SELECT trial of lenvatinib (E7080) that investigated progression free survival (PFS) in people with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC). PFS with lenvatinib was extended significantly compared to placebo (Hazard Ratio (HR)=0.21, [99% CI, 0.14-0.31]; p<0.0001). The median PFS with lenvatinib and placebo were 18.3 months and 3.6 months, respectively. The statistically significant PFS benefit for lenvatinib was confirmed in all predefined subgroups of the study. ^[ ^1]  These data will be presented at the 50 ^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in a Head and Neck Cancer oral session on Monday 2 June (Abstract No. LBA6008), and as part of the official press programme on Saturday 31 May. ^[ ^1 ^]  Differentiated thyroid cancer is the most common form of thyroid cancer and accounts for approximately 90% of all thyroid cancers. ^[2] Currently there are very few effective therapies for RR-DTC in Europe. Lenvatinib is an oral multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors, in addition to other proangiogenic and oncogenic pathway-related RTKs involved in tumour proliferation. ^[3]   "These results show the benefit of lenvatinib in this rare, hard-to-treat cancer. Finding a treatment with positive phase III results for this aggressive form of thyroid cancer, where there are currently limited options, will be welcomed by physicians and patients all over the world," commented Professor Martin Schlumberger, Primary Investigator and M.D. Institut Gustave Roussy, University Paris Sud, Paris, France.  PFS was the primary endpoint for this study. Secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety. Rates of complete response were 1.5% (4 patients) for the lenvatinib group and zero in the placebo group. The results for partial response were 63.2% (165 patients) in the lenvatinib group and 1.5% (2 patients) in the placebo arm. The median exposure duration was 13.8 months for lenvatinib and 3.9 months for placebo and the median time to response for lenvatinib was 2.0 months. ^[ ^1 ^] Median OS has not yet been reached.  "Eisai is committed to understanding the potential role of lenvatinib in RR-DTC, an area of oncology with high unmet need. Eisai's first thought is to patients and their families worldwide and these positive phase III results are an important advancement for patients and doctors alike," said Kenichi Nomoto, PhD, President, Oncology Product Creation Unit, Eisai Product Creation Systems.  The five most common lenvatinib treatment-related adverse events (TRAEs) of any grade were hypertension, diarrhoea, decreased appetite, weight loss and nausea. ^[ ^1 ^]  Other abstracts submitted to ASCO reported results for lenvatinib across a variety of tumour types including RR-DTC, non small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC).  Lenvatinib, discovered and developed by Eisai, was granted orphan drug designation (ODD) for the treatment of follicular and papillary thyroid cancer by the European Commission in April 2013. It also has ODD in the United States (U.S.) for follicular, medullary, anaplastic and metastatic or locally advanced papillary thyroid cancer and in Japan for thyroid cancer. Based on these clinical results presented at ASCO, Eisai will submit marketing authorisation applications for lenvatinib to health authorities in the U.S., Japan and Europe.  Notes to Editors   Lenvatinib (E7080)   Lenvatinib, discovered and developed by Eisai, is an oral multiple receptor tyrosine kinase (RTK) inhibitor, with a novel binding mode, that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1 (FLT1), VEGFR2 (KDR) and VEGFR3 (FLT4)), in addition to other proangiogenic and oncogenic pathway-related RTKs (including fibroblast growth factor (FGF) receptors FGFR1, 2, 3 and 4; the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumour proliferation. ^[4] ^, ^[5] It is currently under investigation as a treatment for thyroid, hepatocellular carcinoma (Phase III), non-small cell lung cancer (Phase II) and other solid tumour types.  About SELECT   The SELECT ( S tudy of ( E 7080) LE nvatinib in Differentiated C ancer of the T hyroid) study was a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of patients with RR-DTC and radiographic evidence of disease progression within the prior 13 months, treated with once-daily, oral lenvatinib (24mg) versus placebo. The study enrolled 392 patients in over 100 sites in Europe, North and South America and Asia and was conducted by Eisai in collaboration with the SFJ Pharmaceuticals Group.  Participants were stratified by age (≤65, >65 years), region and ≤1 prior VEGFR-targeted therapies and randomised 2:1 to either lenvatinib or placebo therapy (24mg/d, 28-d cycle). The primary endpoint was PFS assessed by independent radiologic review. The secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety.  The five most common lenvatinib treatment-related adverse events (TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%), decreased appetite (50.2%), weight loss (46.4%) and nausea (41.0%). TRAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) included hypertension (41.8%), proteinuria (10.0%), weight loss (9.6%), diarrhea (8.0%), and decreased appetite (5.4%).  About Thyroid Cancer   Thyroid cancer refers to cancer that forms in the tissues of the thyroid gland, located at the base of the throat near the trachea. ^[6] It is more common in women than in men and most are in their 40s or 50s at time of diagnosis. ^[ ^6 ^] Thyroid cancer is the most common endocrine malignancy and global figures show that its incidence has increased significantly over the last 50 years. ^[7] In Europe alone, almost 63,000 cases of thyroid cancer were diagnosed in 2012. ^[8]  The most common types of thyroid cancer, papillary and follicular (including Hurthle cell), are classified as differentiated thyroid cancer (DTC) and account for approximately 90% of all cases. ^[ ^2 ^] The remaining cases are classified as either medullary (5-7% of cases) or anaplastic (1-2% of cases). ^[9] While most people with DTC are curable with surgery and radioactive iodine treatment, the prognosis for those people who do respond is poor. ^[10] There are limited treatment options for this difficult-to-treat, life-threatening and treatment-refractory form of thyroid cancer. ^[11]  Eisai in Oncology   Our commitment to meaningful progress in oncology research, built on scientific expertise, is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, and biologic and supportive care agents for cancer across multiple indications.  About Eisai   Eisai is one of the world's leading research and development (R&D) based pharmaceutical companies and we define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call human health care ( hhc ).  Eisai concentrates its R&D activities in three key areas:    *Oncology including: anticancer therapies; tumour regression, tumour     suppression, antibodies, etc.   *Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight     loss   *Vascular/Immunological reaction including: thrombocytopenia, rheumatoid     arthritis, psoriasis, inflammatory bowel disease  With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 10,000 people worldwide. From its EMEA Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to include Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Czech Republic, Slovakia, the Netherlands, Belgium, Luxembourg, Russia and the Middle East.  For further information please visit our web site http://www.eisai.co.uk  References   1. Schlumberger M et al. A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). ASCO 2014 abstract #E450   2. Cooper DS et al. Thyroid. 2009;19(11):1167-1214   3. Data on file, Eisai.Co.Ltd   4. Matsui J, et al. Clin Cancer Res 2008;14:5459-65   5. Matsui J, et al. Int J Cancer 2008;122:664-71   6. National Cancer Institute at the National Institute of Health http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 (last accessed: March 2014)   7. Brito J et al. BMJ 2013; 347   8. Thyroid Cancer. International Agency for Research on Cancer. http://eco.iarc.fr/eucan/Cancer.aspx?Cancer=35 (last accessed: March 2014)   9. Thyroid Cancer Basics. 2011. http://www.thyca.org   10. Gild M et al. Nature Reviews Endocrinology. 2011;7:617-624   11. Bible K, et al. Lancet Oncology 2010;11(10):962-972     Job code: Lenvatinib-UK0023  Date of preparation: May 2014  Contact: Media Enquiries: Eisai Europe Ltd, Cressida Robson / Charlotte Andrews, +44(0)7908-314-155/+44(0)7947-231-513, Cressida_Robson@eisai.net, Charlotte_Andrews@eisai.net; Tonic Life Communications, Siobhan Reilly / April Kenneally, +44(0)207-798-9999 /+44(0)207-798-9263, siobhan.reilly@toniclc.com, april.kenneally@toniclc.com  
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