Overall Survival Gain With Lenvima® (Lenvatinib) in Advanced Thyroid Cancer Presented by Eisai at European Cancer Congress (ECC) 2015

HATFIELD, England, September 14, 2015 /PRNewswire/ --


Clinicians also present data confirming efficacy and safety of Halaven(R) (eribulin)

in metastatic breast cancer 

Eight abstracts which highlight new study results in oncology will be presented at the 18th Biennial Congress of European Cancer Congress (ECC), Vienna, 25 September to 29 September 2015.

Overall survival gain with lenvatinib in radioactive iodine refractory differentiated thyroid cancer (RAI Refractory-DTC) versus placebo, from a new analysis from the Phase III SELECT study, will be presented to the conference as part of an oral session on Saturday 26 September 2015.

A new analysis of serum biomarkers and clinical outcomes in the Phase II study of lenvatinib, everolimus and the combination in the treatment of metastatic renal cell carcinoma will be presented as part of a poster session on 26 September 2015. This study was originally presented as part of an oral presentation at the American Society of Clinical Oncology Annual Meeting (ASCO) in May 2015.

Data on the influence of time to objective response on lenvatinib clinical outcomes in the SELECT study will be presented as a poster on Sunday 27 September 2015.  Data on the efficacy and safety of lenvatinib by 131I-refractory criteria in the SELECT trial will also feature as a poster on the same day.

"With these data, Eisai stands up for people with rare, metastatic and advanced cancers. Through innovation, and a focus on extending the lives of people with cancer Eisai is proud to present these results at the European Cancer Congress 2015," comments Gary Hendler, President and CEO Eisai EMEA and President, Eisai Oncology Global Business Unit.

Further health-related quality of life results from the Phase III study in which eribulin was compared to dacarbazine, in people with soft tissues sarcomas subtypes will also be presented as a poster on Saturday 26 September 2015.

In July 2015, a Type II variation application was submitted in the European Union to indicate eribulin for the treatment of patients with inoperable soft tissue sarcoma who have already received chemotherapy for locally advanced or metastatic disease. Similar applications have also been submitted in the US and Japan.

Further abstracts from investigator initiated studies in eribulin in metastatic breast cancer will be presented at the congress.

A summary of the Eisai abstracts accepted for presentation at this year's ECC meeting can be found below:

Product Abstract Name Session

Lenvatinib Overall survival gain with Abstract No: 2805
lenvatinib vs. placebo in 26 September 2015
radioactive iodine refractory Oral: 10:30 - 12:50 CEST,
differentiated thyroid cancer Hall C1
(RR-DTC): An updated analysis Guo, M.

Lenvatinib Correlative analyses of serum Abstract No: 432
biomarkers and clinical outcomes in 26 September 2015
the phase 2 study of lenvatinib, Poster: 16:45 - 18:45
everolimus, and the combination, in CEST, Hall C
patients with metastatic renal cell Glen, H.
carcinoma following 1 VEGF-targeted

Lenvatinib The influence of time to objective Abstract No: 2862
response on lenvatinib clinical 27 September 2015
outcomes in the phase 3 SELECT trial Poster: 9:15 - 11:15 CEST,
Hall C
Newbold, K.

Lenvatinib Defining 131I-refractory Abstract No: 2864
differentiated thyroid cancer: 27 September 2015
efficacy and safety of lenvatinib by Poster: 9:15 - 11:15 CEST,
131I-refractory criteria in the Hall C
SELECT trial Kiyota, N.

Eribulin Randomized, open-label, multicenter, Abstract No: 3441
phase 3 study of eribulin versus 26 September 2015
dacarbazine in patients with Poster: 16:45 - 18:45
leiomyosarcoma and adipocytic CEST, Hall C
sarcoma: Health-related quality of Gelderblom, H.
life results
Eribulin Italian observational study of Abstract No: 1849
Eribulin Mesylate in patients with 28 September 2015
advanced breast cancer: ESEMPiO 09:15 - 11:15 CEST, Hall C
study Barni, S.

Eribulin Activity and toxicity profile of Abstract No: 1865
eribulin mesylate in heavily 28 September 2015
pretreated metastatic breast cancer: Poster: 09:15 - 11:15
An observational study (EVHALAVEN) CEST, Hall C
Patsouris, A.
Eribulin Eribulin mesylate in metastatic Abstract No: 1320
breast cancer, a focus on safety and 28 September 2015
efficacy in elderly patients. Poster. 16.45-18.45, Hall
Results from the EVHALAVEN C
multicentric retrospective cohort Martin-babau,J

Lenvatinib received Marketing Authorisation from the European Commission in May 2015 for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Huerthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).

Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, Europe, Switzerland and Japan, and has been submitted for regulatory approval in South Korea, 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.

Eribulin is currently indicated for the treatment of women with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.[1]

Notes to Editors  

Lenvatinib (E7080) 

Lenvatinib simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumour angiogenesis and proliferation of thyroid cancer.[2],[3] This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR 1-4 as well as VEGFR 1-3. Lenvatinib will be indicated for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Huerthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).[4]

About Lenvatinib's Novel Binding Mode (Type V)[5]  

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.

About SELECT[6] 

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 RR- radioiodine-refractory differentiated thyroid cancer 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, diarrhea, fatigue, decreased appetite, weight loss and nausea. TRAEs of Grade 3 or higher included hypertension, proteinuria, weight loss, diarrhea, and decreased appetite.

Subgroup analyses presented at the European Thyroid Association Annual Meeting in September 2014 showed that lenvatinib maintained a PFS benefit in all pre-defined subgroups of people with progressive radioiodine-refractory differentiated thyroid cancer. In particular, the PFS benefit observed in 195 people with progressive radioiodine-refractory differentiated thyroid cancer in Europe (lenvatinib n=131 and placebo n=64) was similar to the PFS of overall study population (HR=0.24, [95% CI, 0.16-0.35]).[7] The median PFS with lenvatinib and placebo were 18.7 months and 3.7 months respectively.[7]

Two recent subanalyses from the SELECT study have been presented at the Endocrine Society Congress 2015 (ENDO). The first reports the results of the open-label extension phase of SELECT and aims to assess the crossover of patients in the placebo arm to the optional open-label lenvatinib treatment period. The results highlight that patients who crossed over from the placebo arm achieved a median PFS of 12.4 months with open-label lenvatinib treatment. Although toxicities were substantial, these were generally managed with medications, dose interruption, and dose reductions.[8]

The second abstract examines the relationship between thyroid abnormalities and their effect on the safety and efficacy outcomes in SELECT. The analysis shows that although an increase in thyroid-stimulating hormone (TSH) levels was a frequent complication, its direct relationship to lenvatinib therapy has not been established and there is no evidence TSH levels affect tumour responses to lenvatinib treatment.[9]

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.[10] It is more common in women than in men and most are in their 40s or 60s at time of diagnosis.[11]

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.[12] 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.[13] The remaining cases are classified as either medullary (5-7% of cases) or anaplastic (1-2% of cases).[14]

RR-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.[13] There are limited treatment options for this life-threatening and treatment-refractory form of thyroid cancer.[14]

About Renal Cell Carcinoma 

Renal cell carcinoma (RCC) is the most common form of kidney cancer. The standard treatment for metastatic or advanced renal cell carcinoma is molecular targeted drug therapy, which is designed to interfere with the specific molecules necessary for tumour growth and progression. Despite this, it remains a disease for which patients have very few treatment options.[15]

RCC originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. This form of cancer also arises from the cortical collecting ducts in addition to the proximal tubule. The only tumours of the kidney that are not included in the definition of RCC are tumours of the renal pelvis and ureters.

RCC accounts for approximately 90% of all kidney malignancies and represents an estimated 2-3% of all cancer cases, with the highest incidence occurring in Western countries. During the last two decades, until recently, there has been an annual 2% increase in incidence of the disease worldwide.[16]

Halaven(R) (eribulin)  

Eribulin is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division.[1]

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 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.  


1.  SmPC Halaven (updated June 2015). Available at:  http://www.medicines.org.uk/emc/medicine/24382/SPC/Halaven+0.44+mg+ml+solution+for+injection Accessed:July 2015

2.  Matsui J et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res 2008 Sep 1;14(17) :5459-65.

3.  Matsui J et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. 2008 Feb 1;122(3):664-71.

4.  SmPC Lenvima (updated May 2015). Available at: www.medicines.org.uk/emc/medicine/30412 [http://www.medicines.org.uk/emc/medicine/30412 ] . Accessed: September 2015

5.  Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Med. Chem. Lett 2015;6:89-94

6.  Schlumberger M et al. Lenvatinib versus placebo in radioiodine refractory differentiated thyroid cancer. NEJM 2015; 372: 621-630. Available at http://www.nejm.org/doi/full/10.1056/NEJMoa1406470 Accessed: August 2015

7.  Newbold K et al. Phase 3 study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT): Results and subgroup analysis of patients from Europe. Presented as a digital poster at ETA 2014. 

8.  Wirth L et al. 2015; Open-Label Extension Phase Outcomes of the Phase 3 Select Trial of Lenvatinib in Patients with 131I-Refractory Differentiated Thyroid Cancer. Endocrine Reviews; 36;2: Abstract 0R44-6. Available at: http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2015.THPTA.6.OR44-6 Accessed: September 2015

9.  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: September 2015

10. National Cancer Institute at the National Institute of Health. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 . Accessed: August 2015

11. Brito J et al. BMJ 2013; 347

12. Cancer Research UK. Thyroid Cancer Incidence Statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/thyroid/incidence/uk-thyroid-cancer-incidence-statistics Accessed: June 2015

13. Gild M et al. Multikinase inhibitors: a new option for the treatment of thyroid cancer. Nature Reviews Endocrinology. 2011; 7: 617-624

14. Thyroid Cancer Basics. 2011. Available at: www.thyca.org [http://www.thyca.org ] . Accessed: August 2015

15. National Cancer Institute at the National Institute of Health. Available at: http://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq . Accessed: August 2015

16. Ljungberg et al. Guidelines on Renal Cell Carcinoma. Available at: http://uroweb.org/wp-content/uploads/10-Renal-Cell-Carcinoma_LR-LV2-2015.pdf . Accessed: August 2015

Date of preparation: September 2015

Job code: Oncology-UK0046




CONTACT: Eisai, Cressida Robson / Ben Speller, +44(0)7908-314-155 /+44(0)7947-231-513, Cressida_Robson@eisai.net, Ben_Speller@eisai.net ;Tonic Life Communications, Alex Davies / Emma Coughlan, +44(0)7720-496-472/ +44(0)7772-534-646, Alex.Davies@toniclc.com,Emma.Coughlan@toniclc.com

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