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.[1] 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).[1] 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).[2]

"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).[3]
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.[3]

Data from a third sub-analysis show that lenvatinib improves
overall survival in older patients with RR-DTC, irrespective of dose
intensity.[4] The analysis shows a significant correlation between
progression-free and overall survival in patients older than 65.[4]
This analysis is of particular importance, as progressive
radioiodine-refractory differentiated thyroid cancer is more common
in older patients.[5]

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.[6]

"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.[7] 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.[8]

Differentiated thyroid cancer is the most common form of thyroid
cancer and accounts for approximately 90% of all thyroid cancers.[9]
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. [10]

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

About Lenvatinib

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)[10],[11]

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[12]

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.[13] It is more common in women than in men and most are in
their 40s or 50s at time of diagnosis.[14]

Thyroid cancer affects more than 52,000 people in Europe each
year.[15] 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.[9] The
remaining cases are classified as either medullary (5-7% of cases) or
anaplastic (1-2% of cases).[16]

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. [15]
There are limited treatment options for this life-threatening and
treatment-refractory form of thyroid cancer.[16]

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

ots Originaltext: Eisai
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