Eisai announces results from Phase III SELECT trial of lenvatinib evaluating PFS in patients with RR-DTC

Eisai Inc. announced today results from the Phase III SELECT trial of investigational agent lenvatinib evaluating progression-free survival (PFS) in patients with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC). Progression-free survival with lenvatinib was extended significantly compared to placebo>th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago as part of the ASCO press conference on May 31 and also in an oral session on Monday, June 2 (Abstract No. LBA6008).

Lenvatinib is an oral, multiple receptor tyrosine kinase inhibitor with a unique binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors, in addition to other proangiogenic and oncogenic pathway-related receptor tyrosine kinases involved in tumor proliferation. The SELECT study confirmed a statistically significant benefit for treatment with lenvatinib on PFS in all predefined subgroups. Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety. The ORR for lenvatinib was significantly increased to 64.8 percent (95% CI: 59.0-70.5) compared to 1.5 percent (95% CI: 0.0-3.6; p<0.0001) in the placebo arm. Median OS has not been reached yet.

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%).

"These results for lenvatinib in patients with treatment-refractory differentiated thyroid cancer are very encouraging," commented Lori Wirth, M.D., Study Investigator and Medical Director of the Center for Head and Neck Cancers at Massachusetts General Hospital. "Treatment options for radioiodine-refractory DTC are limited and there is a major unmet need for new therapies."  

Eisai was granted Orphan Drug Designation (ODD) for lenvatinib in various types of thyroid cancer in the United States, Japan, and Europe and will submit marketing authorization applications to those health authorities.

Eisai is committed to the therapeutic area of oncology and has an ongoing clinical trial program with lenvatinib in various tumor types.

About Lenvatinib 
Lenvatinib, discovered and developed by Eisai, is an oral, multiple receptor tyrosine kinase inhibitor with a unique 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 receptor tyrosine kinases (including fibroblast growth factor [FGF] receptors FGFR1, 2, 3, and 4; the platelet-derived growth factor [PDGF] receptor PDGFRα; KIT; and RET) involved in tumor proliferation. It is currently under investigation in thyroid, hepatocellular, endometrial and other solid tumor types.

SELECT Design Summary
The SELECT (Study of E7080 LEnvatinib in Differentiated Cancer of the Thyroid) study was a multicenter, randomized, 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 12 months, treated with once-daily, oral lenvatinib (24 mg) versus placebo. Secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety. The study enrolled 392 patients at 117 sites in Europe, North and South America and Asia and was conducted by Eisai in collaboration with the SFJ Pharmaceuticals Group.

Patients were stratified by geographic region, prior VEGF/VEGFR targeted therapy (0 vs 1) and age (≤65 years vs >65 years) and randomized at a ratio of 2:1 to receive treatment with either lenvatinib 24 mg/day (administered orally, once a day) or placebo.