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Data Presented at the 15th International Thyroid Congress Provides Further Evidence for Lenvatinib in People with Advanced Thyroid Cancer
Hatfield, England (ots/PRNewswire) - Lenvima(R) (lenvatinib) demonstrates clinically significant progression-free survival in people with advanced thyroid cancer across most of the common sites of metastases
FOR EU MEDIA ONLY: NOT FOR SWISS OR AUSTRIAN JOURNALISTS
Data show Lenvima(R) (lenvatinib) improves progression-free survival for people with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC) regardless of metastatic site, with the exception of the brain. These lenvatinib Phase III SELECT trial sub-analyses were presented at the 15th International Thyroid Congress (ITC) in an oral session on Monday 19 October.
The sub-analysis observed response rates of more than 50% and a progression-free survival benefit among people treated with lenvatinib with common sites of metastasis (bone, liver, lung, lymph node). The study examined 392 patients being treated with lenvatinib vs placebo, and identified metastatic subgroups as an important determinant of progression-free survival for people treated with lenvatinib.
Lenvatinib is currently indicated in Europe for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).
"These encouraging survival data confirm lenvatinib's efficacy profile across different patient sub-populations and metastatic sites. These data also suggest that people with advanced thyroid cancer should be treated with lenvatinib after the development of metastases in order to experience the significant progression-free survival benefit," comments Professor Martin Schlumberger, M.D. Institut Gustave Roussy, University Paris Sud, Paris, France.
A second analysis of the Phase III SELECT study at ITC 2015 demonstrates that lenvatinib maintains progression-free survival irrespective of body mass index, as seen in a sub-analysis of three patient groups: under-and-normal weight (<25kg/m2), overweight (25-29.99 kg/m2), and obese (greater than or equal to30 kg/m2). Obese patients who receive lenvatinib exhibited the greatest progression-free survival versus placebo (median PFS 16.7 months; HR 0.13; 95% CI 0.07-0.24; p<0.0001), but significant improvement in progression-free survival was observed across all subgroups. Similarly lenvatinib showed comparable toxicities across all groups.
Data from a third sub-analysis show that lenvatinib improves overall survival in older patients with RR-DTC, irrespective of dose intensity. The analysis shows a significant correlation between progression-free and overall survival in patients older than 65. This analysis is of particular importance, as progressive radioiodine-refractory differentiated thyroid cancer is more common in older patients.
Results from an indirect analysis of the numbers needed to treat (NNT) for lenvatinib and sorafenib in the SELECT and DECISION trials respectively will also be presented at ITC 2015. Against placebo, the NNT at 24 months for 1 patient to achieve PFS was 2.5 for lenvatinib and 10.9 for sorafenib; OS was 11.5 for lenvatinib and 41.7 for sorafenib.
"These data from the indirect comparison between studies suggest there is an advantage in treatment with lenvatinib over sorafenib in achieving both progression-free and overall survival in patients with this hard-to-treat cancer. Our continuing work in the evaluation of survival in RAI-R DTC and the ongoing accrual of knowledge about lenvatinib in this disease reflects our strong commitment to the oncology community," comments Dr Alton Kremer, Deputy President, Oncology PCU and Chief Medical Officer, Global Oncology Business Unit, Eisai Inc.
Further SELECT sub-analyses presented at ITC 2015 examine the relationship between treatment-related adverse events such as hypertension and diarrhoea for lenvatinib. One analysis demonstrates that common adverse events for people who are treated with lenvatinib typically occur early during treatment and can primarily be managed with dose modification. A second analysis found that female gender, baseline hepatic impairment, and a lower number of metastatic sites may be associated with a higher likelihood of developing treatment-emergent hypertension (TE-HTN) in patients treated with lenvatinib.
Differentiated thyroid cancer is the most common form of thyroid cancer and accounts for approximately 90% of all thyroid cancers. 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. 
Abstract Name Session Lenvatinib Abstracts Outcomes by Site of Metastasis for Patients Poster #55 With Radioiodine-refractory Differentiated Oral presentation Thyroid Cancer Monday, October 19 4:00 p.m. - 4:30 p.m. Treated With Lenvatinib Versus Placebo: Poster: Monday, October 19 Results from a Phase 3, Randomized Trial 9:20 a.m. - 9:45 a.m.; 3:05 p.m. - 4:00 p.m Tuesday, October 20 9:20 a.m. - 9:45 a.m. Habra M. Lenvatinib and the Effect of Age on Overall Poster #731 Survival Poster presentation for Patients With Radioiodine-refractory Wednesday, October 21 Differentiated Thyroid Cancer 9:20 a.m. - 9:45 a.m.; 3:05 p.m. - 4:00 p.m. Thursday, October 22 9:20 a.m. - 10:20 a.m. Brose M. Characteristics of Patients on Lenvatinib Poster #629 With Treatment-emergent Hypertension in the Poster presentation SELECT Trial Wednesday, October 21 9:20 a.m. - 9:45 a.m., 3:05 p.m. - 4:00 p.m. Thursday, October 22 9:20 a.m. - 10:20 a.m Rietschel P. Efficacy and Safety of Lenvatinib by Body Poster #693 Mass Index in Patients With 131I-Refractory Poster presentation Differentiated Thyroid Cancer From the Phase Wednesday, October 21 3 SELECT Study 9:20 a.m. - 9:45 a.m.; 3:05 p.m - 4:00 p.m. Thursday, October 22 9:20 a.m. - 10:20 a.m. Tahara M. Incidence and Timing of Common Adverse Events Poster #647 in Lenvatinib-treated Patients With Poster presentation Radioiodine-refractory Thyroid Cancer From Wednesday, October 21 the SELECT Trial 9:20 a.m. - 9:45 a.m.; 3:05 p.m. - 4:00 p.m. Thursday, October 22 9:20 a.m. - 10:20 a.m. Gianoukakis A. Number-Needed-to-Treat (NNT) Analysis of Poster #670 Therapies In Radioiodine-refractory Poster presentation Differentiated Thyroid Cancer (RR-DTC) Using Wednesday, October 21 Indirect Comparison 9:20 a.m. - 9:45 a.m.; 3:05 p.m. - 4:00 p.m. Thursday, October 22 9:20 a.m. - 10:20 a.m. Tremblay G. RAI-R DTC Quality of Survival Abstract A Study of the Quality of Survival in Poster #231 Radioiodine Refractory Thyroid Cancer Poster presentation Monday, October 19 Poster: Monday, October 19 9:20 a.m. - 9:45 a.m.; 3:05 p.m. - 4:00 p.m. Tuesday, October 20 9:20 a.m. - 9:45 a.m. Taylor M.
Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, South Korea, Europe and Japan, and has been submitted for regulatory approval in Switzerland, Canada, Singapore, Russia, Australia and Brazil. Lenvatinib was granted Orphan Drug Designation in Japan for thyroid cancer, in the United States for treatment of follicular, medullary, anaplastic, and metastatic or locally advanced papillary thyroid cancer and in Europe for follicular and papillary thyroid cancer.
The development of lenvatinib underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and well-being of people worldwide. Eisai is committed to the therapeutic area of oncology and to address the unmet medical needs of patients and their families.
Notes to Editors
Eisai is currently conducting clinical studies of lenvatinib in several types of cancer including hepatocellular carcinoma (Phase III), renal cell carcinoma (Phase II), non-small cell lung cancer (Phase II) and endometrial cancer (Phase II).
About Lenvatinib's Novel Binding Mode (Type V),
Kinase inhibitors are categorized into several types (Type I to Type V) depending on the binding site and the conformation of the targeted kinase in complex with them. Most of the currently approved tyrosine kinase inhibitors are either Type I or Type II, however according to X-ray crystal structural analysis, lenvatinib was found to possess a new Type V binding mode of kinase inhibition that is distinct from existing compounds. In addition, lenvatinib was confirmed via kinetic analysis to exhibit rapid and potent inhibition of kinase activity, and it is suggested that this may be attributed to its novel binding mode.
The SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) study was a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of patients with 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 (less than or equal to65, >65 years), region and less than or equal to1 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. 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. Median OS has not yet been reached.
The six most common lenvatinib treatment-related adverse events (TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%), fatigue (59.0%), decreased appetite (50.2%), weight loss (46.4%) and nausea (41.0%). TRAEs of Grade 3 or higher included hypertension (41.8%), proteinuria (10.0%), weight loss (9.6%), diarrhoea (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. It is more common in women than in men and most are in their 40s or 50s at time of diagnosis.
Thyroid cancer affects more than 52,000 people in Europe each year. The incidence of thyroid cancer has increased significantly in the last decade by 69% and 65% in men and women, respectively. 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. The remaining cases are classified as either medullary (5-7% of cases) or anaplastic (1-2% of cases).
RAI Refractory-DTC is a rare, difficult-to-treat type of cancer, characterised by aggressive growth and spread. While most DTC patients are curable with surgery and radioactive iodine treatment, the prognosis for those patients who do not respond is poor.  There are limited treatment options for this life-threatening and treatment-refractory form of thyroid cancer.
About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. 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 our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology.
As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.
For more information about Eisai Co., Ltd., please visit http://www.eisai.com.
References 1. Habra, MA et al. Outcomes by Site of Metastasis for Patients With Radioiodine-refractory Differentiated Thyroid Cancer Treated With Lenvatinib Versus Placebo: Results from a Phase 3, Randomized Trial. 15th International Thyroid Congress 2015; Presented at the 15th International Thyroid Congress, October 2015 2. SmPC Lenvima (updated June 2015). Available at: http://www.medicines.org.uk/emc/medicine/30412 . Accessed: October 2015 3. Tahara, M et al. Efficacy and Safety of Lenvatinib by Body Mass Index in Patients With 131I-Refractory Differentiated Thyroid Cancer From the Phase 3 SELECT Study. 15th International Thyroid Congress 2015; Presented at the 15th International Thyroid Congress, October 2015 4. Brose, M et al. Lenvatinib and the Effect of Age on Overall Survival for Patients With Radioiodine-refractory Differentiated Thyroid Cancer. 15th International Thyroid Congress 2015, October 2015 5. Haymart, R et al. Understanding the Relationship Between Age and Thyroid Cancer. The Oncologist 2009; 14: 216-221 6. Tremblay, G et al. Number-Needed-to-Treat (NNT) Analysis of Therapies In Radioiodine-refractory Differentiated Thyroid Cancer (RR-DTC) Using Indirect Comparison. 15th International Thyroid Congress 2015; Presented at the 15th International Thyroid Congress, October 2015 7. Haddad, R et al. Incidence and Timing of Common Adverse Events in Lenvatinib-treated Patients With Radioiodine-refractory Thyroid Cancer From the SELECT Trial. 15th International Thyroid Congress 2015; Presented at the 15th International Thyroid Congress, October 2015 8. Abouzaid, S et al. Characteristics of Patients on Lenvatinib With Treatment-emergent Hypertension in the SELECT Trial. 15th International Thyroid Congress 2015, October 2015 9 . Thyroid Cancer Basics. 2011. Available at: http://www.thyca.org. Accessed: October 2015 10. Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Med. Chem. Lett 2015; 6:89-94 11. Wu P et al. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discovery Today 2015; 1-6 12 . Schlumberger M, et al. Relationship Between Thyroid-Stimulating Hormone Levels and Outcomes from the Randomized, Double-Blind, Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT). Available at: https://endo.confex.com/endo/2015endo/webprogram/Paper20459.html. Accessed: October 2015 13. Brito J et al. BMJ 2013; 347 14. Cabanillas ME, Dadu R. Optimizing therapy for radioactive iodine-refractory differentiated thyroid cancer : Current state of the art and future directions. Minerva Endocrinol. 2012 Dec; 37(4):335-356. 15 . EUCAN 2015. http://eu-cancer.iarc.fr/EUCAN/Cancer.aspx?Cancer=35. Accessed: October 2015 16. Pacini F et al. ESMO Guidelines Working Group. Ann Oncol. 2012;23 (suppl 7):vii110-vii119.
Date of preparation: October 2015 Job code: Oncology-UK0064
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