Clinical Trials

Date: 2015-09-27

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the European Cancer Congress (ECC), Vienna

Company: Eisai (Japan)

Product: lenvatinib

Action mechanism:

tyrosine kinase inhibitor/kinase inhibitor. Lenvatinib is an oral molecular targeted agent that selectively inhibits the activities of several different molecules including vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), RET, KIT and platelet-derived growth factor receptors (PDGFR). It simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumour angiogenesis and proliferation of thyroid cancer. This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR 1-4 as well as VEGFR 1-3. 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. 

Discovered and developed by Eisai, lenvatinib received accelerated European Medicines Agency (EMA) review on the 31 July and was filed in Europe and the U.S. on 18 August 2014. The FDA granted approval to Lenvima® (lenvatinib) to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease progressed despite receiving radioactive iodine therapy (radioactive iodine refractory disease) on February 13, 2015.

Lenvatinib was granted orphan drug designation (ODD) for the treatment of follicular and papillary thyroid cancer by the European Commission in April 2013.

Disease: thyroid cancer

Therapeutic area: Cancer - Oncology

Country:

Trial details:

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 (?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.

Latest news:

* On February 13, 2015, Eisai announced that the New England Journal of Medicine (NEJM) has published pivotal results from the Phase III SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) trial of lenvatinib (E7080) in the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC) (Schlumberger M et al. Lenvatinib versus placebo in radioiodine refractory differentiated thyroid cancer). The results demonstrate that lenvatinib significantly extended progression-free survival (PFS) by a median of 14.7 months (Hazard Ratio (HR)=0.21, [99% CI, 0.14-0.31]; p<0.001). Further results from the study, published  in the New England Journal of Medicine (NEJM), show that lenvatinib improves response rate (64.8%) for people with radioiodine-refractory differentiated thyroid cancer compared with placebo (1.5%).

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. New 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]).[9] The median PFS with lenvatinib and placebo were 18.7 months and 3.7 months respectively. 

For lenvatinib, treatment-related adverse effects (>40%, all grades) were hypertension (67.8%), diarrhoea (59.4%), fatigue (59.0%), decreased appetite (50.2%), decreased weight (46.4%), and nausea (41.0%). Adverse effects were managed with dose reductions and standard interventions and were greater with lenvatinib, and include six (2.3%) treatment-related deaths.

Is general: Yes