Significant Improvement in Progression-Free Survival With Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer: Data Confirmed in New Subgroup Analyses

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Eisai Europe Limited

06 Sep, 2014, 22:01 GMT

HATFIELD, England, September 6, 2014 /PRNewswire/ --

FOR EMEA MEDIA ONLY: NOT FOR SWISS MEDIA 

New subgroup analyses in patients with lung and bone metastases to be presented at the European Thyroid Association 38th Annual Meeting 

Data from the Phase III Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT) show that Progression Free Survival (PFS) with lenvatinib is extended significantly compared to placebo 18.3 months vs 3.6 months, in people with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC) (Hazard Ratio (HR)=0.21, [95% CI, 0.14-0.31]; p<0.0001). Exploratory subgroup analyses from the SELECT trial to be presented today at the 38th Annual Meeting of the European Thyroid Association, suggest that lenvatinib maintains PFS benefit in people with progressive RR-DTC including people with lung metastasis, median PFS: lenvatinib, 18.7 months; placebo, 3.6 months (HR=0.21, [95% CI, 0.15-0.29]; p<0.0001), and bone metastasis median PFS: lenvatinib, NR; placebo, 7.4 months (HR=0.65, [95% CI, 0.11-4.07] p<0.0001).[1]

A second subgroup analysis of the SELECT data, to be presented at the annual meeting, finds that the PFS benefit is similar in 195 people in Europe with progressive RR-DTC (lenvatinib n=131 and placebo n=64) compared with the overall study population (HR=0.24, [95% CI, 0.16-0.35]; p<0.0001).[2] The median PFS with lenvatinib and placebo is 18.7 months and 3.7 months respectively.  

"The data from our subgroup analyses are consistent with the overall SELECT study and show that lenvatinib is effective in this rare and hard-to-treat cancer. We are excited to present these subgroup analyses at this European forum, as patients and physicians across Europe are in urgent need of options to treat this aggressive form of thyroid cancer," commented Kate Newbold, Primary Investigator and Consultant Clinical Oncologist at The Royal Marsden Hospital NHS Foundation Trust, UK.

Thyroid cancer is the most common endocrine malignancy.[3] In Europe alone, over 50,000 cases of thyroid cancer were diagnosed in 2012.[4] Although treatment is possible for most types of thyroid cancer, there remains an unmet need for treatment options for thyroid cancer once the disease has progressed.

Lenvatinib is an oral multiple tyrosine kinase inhibitor (TKI) with a novel binding mode that selectively inhibits the kinase activities of all vascular endothelial growth factor receptors (VEGFR), in addition to other proangiogenic and oncogenic pathway-related RTKs including all fibroblast growth factor receptors (FGFR), the platelet-derived growth factor (PDGF) receptor PDGFRα, KIT and RET that are involved in tumour proliferation. This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR1-4 as well as VEGFR1-3.[5],[6],[7]

The SELECT study was a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of people with RR-DTC and radiographic evidence of disease progression within the prior 13 months, treated with once-daily, oral lenvatinib (24mg) versus placebo.[8] Secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety. 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.

The 5 most common treatment-related adverse events (any grade) in the European subgroup were hypertension (68%), diarrhoea (59%), decreased appetite (50%), decreased weight (46%) and nausea (41%).

Lenvatinib, discovered and developed by Eisai, received accelerated European Medicines Agency (EMA) review on the 31 July and was filed in Europe and the U.S. on 18 August 2014. Lenvatinib was filed in Japan in June 2014. Lenvatinib 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 for follicular, medullary, anaplastic and metastatic or locally advanced papillary thyroid cancer in the U.S. and thyroid cancer in Japan.

The development of lenvatinib underscores Eisai's human health care 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 addressing the unmet medical needs of patients and their families.

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 all vascular endothelial growth factor receptors (VEGFR), in addition to other proangiogenic and oncogenic pathway-related RTKs including all fibroblast growth factor receptors (FGFR), the platelet-derived growth factor (PDGF) receptor PDGFRα, KIT and RET that are involved in tumour proliferation.[9],[10] This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR as well as VEGFR. 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[8]

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-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. 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.

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.[11] It is more common in women than in men and most are in their 40s or 50s at time of diagnosis.[3] Thyroid cancer is the most common endocrine malignancy and global figures show that its incidence has increased significantly over the last 50 years.[3]

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.[12] The remaining cases are classified as either medullary (5-7% of cases) or anaplastic (1-2% of cases).[13]While most DTC patients are curable with surgery and radioactive iodine treatment, the prognosis for those patients who do not respond is poor.[14] There are limited treatment options for this difficult-to-treat, life-threatening and treatment-refractory form of thyroid cancer.[15]

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 management
  • 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 Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Iceland, Ireland, Italy, the Middle East, the Netherlands, Norway, Portugal, Russia, Slovakia, Spain, Switzerland, Sweden, and the United Kingdom.

For further information please visit our web site: http://www.eisai.co.uk

References 

  1. Sherman S et al. Subgroup analyses of a phase 3, multicentre, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). Presented as an oral presentation at ETA 2014
  2. 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
  3. Brito J et al. BMJ 2013; 347
  4. Thyroid Cancer. International Agency for Research on Cancer. http://eco.iarc.fr/eucan/Cancer.aspx?Cancer=35 (last accessed: September 2014)
  5. Data on file, Eisai.Co.Ltd
  6. Zuccotto F et al. J. Med. Chem. 2010, 53, 2681-2694.
  7. Liao et al. Journal of Medicinal Chemistry, 2007, 50;3:409-422
  8. 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
  9. Matsui J, et al. Clin Cancer Res 2008;14:5459-65
  10. Matsui J, et al. Int J Cancer 2008;122:664-71
  11. National Cancer Institute at the National Institute of Health http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 (last accessed: September 2014)
  12. Cooper DS et al. Thyroid. 2009;19(11):1167-1214
  13. Thyroid Cancer Basics. 2011. http://www.thyca.org
  14. Gild M et al. Multikinase inhibitors: a new option for the treatment of thyroid cancer. Nature Reviews Endocrinology. 2011; 7: 617-624
  15. Bible K, et al. Lancet Oncology 2010;11(10):962-972

Job code: Lenvatinib-UK0033
Date of preparation: September 2014