The FDA ( Food and Drug Administration ) has approved novel anticancer agent Lenvima ( Lenvatinib mesylate ) as a treatment for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer ( RAI-R DTC ).
Lenvima was granted priority review status by the FDA, and was ultimately approved six months from the submission of the New Drug Application in August 2014, two months ahead of the FDA priority review action date.
Lenvima is an orally administered molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR. In particular, the agent simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumor angiogenesis and proliferation of thyroid cancer.
Furthermore, Lenvima has been confirmed through X-ray crystal structural analysis to be the first compound to demonstrate a new binding mode ( type V ) to VEGFR2, and exhibits rapid and potent inhibition of kinase activity, according to kinetic analysis.
The approval was based on the results of a multicenter, randomized, double-blind, placebo-controlled phase III study ( SELECT study ) of 392 patients with progressive RAI-R DTC.
In the study's primary endpoint of progression-free survival ( PFS ), Lenvima has demonstrated a statistically significant extension in PFS compared to placebo ( p less than 0.001; median PFS in the Lenvima group: 18.3 months, median PFS in the placebo group: 3.6 months; hazard ratio, HR=0.21 [ 99% CI: 0.14-0.31] ).
In addition, Lenvima has demonstrated a statistically significant improvement in response rate ( sum of complete and partial responses ) compared to placebo ( p less than 0.001; Lenvima: 64.8% vs placebo: 1.5% ).
In particular, complete response was observed in 1.5% ( 4 patients ) of the Lenvima group and zero in the placebo group.
The most common Lenvima treatment-related adverse events of any grade, which occurred in more than 40% of patients in the Lenvima group, were hypertension ( 67.8% ), diarrhea ( 59.4% ), fatigue or asthenia ( 59.0% ), decreased appetite ( 50.2% ), weight loss ( 46.4% ) and nausea ( 41.0% ).
The number of patients newly diagnosed with thyroid cancer in 2012 in the United States was estimated to be approximately 52,000. Although treatment is possible for most types of thyroid cancer, there are few treatment options available once thyroid cancer has progressed. ( Xagena )
Source: Eisai, 2015