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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