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FDA Approval Sought for Thyroid Cancer Drug Lenvatinib

Treatment improves progression-free survival versus placebo

An application has been submitted to the FDA for marketing approval of the anticancer agent lenvatinib mesylate as a treatment for progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC).

Lenvatinib is an oral multiple-receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of several different RTKs involved in angiogenesis and tumor proliferation, including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor-alpha (PDGFR-alpha). According to the drug’s developer (Eisai Co., Ltd.), this potentially makes lenvatinib a first-in-class treatment in thyroid cancer, especially given that it simultaneously inhibits the kinase activities of VEGFR and FGFR.

The marketing application was based on data from the phase III randomized, double-blind, placebo-controlled SELECT (Study of [E7080] LEnvatinib in Differentiated Cancer of the Thyroid) trial, which evaluated lenvatinib in 392 patients with RR-DTC and radiographic evidence of disease progression within the previous 13 months. The patients may have received one or more prior VEGFR-targeted therapies.

Compared with placebo, lenvatinib achieved a statistically significant improvement (hazard ratio = 0.21; P < 0.0001) in progression-free survival (PFS) — the study’s primary endpoint. The median PFS with lenvatinib was 18.3 months compared with 3.6 months with placebo.

Secondary endpoints included the overall response rate (ORR; the sum of the complete response rate and the partial response rate), overall survival (OS), and safety. The ORR was 64.8% with lenvatinib compared with 1.5% with placebo. A complete response was observed in 1.5% of the lenvatinib group compared with 0% of the placebo group. The median time to response for lenvatinib was 2.0 months. Median OS has not been reached in either group.

The most common treatment-related adverse events (TRAEs; events with an incidence rate of at least 40%) associated with lenvatinib included hypertension (67.8%), diarrhea (59.4%), decreased appetite (50.2%), weight loss (46.4%), and nausea (41.0%). The most common TRAEs (events with an incidence rate of at least 5%) of grade 3 or higher included hypertension (41.8%), proteinuria (10.0%), weight loss (9.6%), diarrhea (8.0%), and decreased appetite (5.4%).

Lenvatinib is currently under development as a potential treatment for hepatocellular carcinoma (phase III), non–small–cell lung cancer (phase II), and other solid tumor types.

Source: Eisai; August 18, 2014.

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