The U.S. Food and Drug Administration has granted priority review designation to lenvatinib (marketed under the brand name Lenvima by Eisai Inc.) for use in combination with everolimus for the treatment of patients with unresectable advanced or metastatic renal cell carcinoma (RCC), who have been treated with one prior vascular endothelial growth factor (VEGF)-targeted therapy. Lenvatinib is a multiple receptor tyrosine kinase inhibitor that inhibits VEGFR1-3, as well as the other receptor tyrosine kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor receptors, the platelet derived growth factor receptor alpha (PDGFR[alpha]), KIT, and RET.
If the lenvatinib-everolimus combination is approved, it will be the first time a combination of a tyrosine kinase inhibitor and an mTOR inhibitor will be available for patients with unresectable advanced or metastatic renal cell carcinoma following a prior VEGF therapy, according to Eisai.
The FDA's priority review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for lenvatinib for this indication is in the second quarter of this year, according to Eisai.
The decision for approval for the combination will be based on data from a Phase II, three-arm study that compared treatment with lenvatinib and everolimus with treatment with everolimus alone with treatment with lenvatinib alone in a total of 153 patients with advanced or metastatic, clear-cell, renal cell carcinoma. Progression-free survival for the patients receiving the combination was 14.6 months-versus 5.5 months for patients treated with everolimus alone and 7.4 months for patients treated with lenvatinib alone, according to the data published in The Lancet Oncology (2015;16:1473-1482).
Lenvatinib previously received the FDA's breakthrough therapy designation for this RCC indication (OT 8/25/15 issue). Also, lenvatinib has previously been approved by the FDA for the treatment of patients with differentiated thyroid cancer (DTC) whose disease has progressed despite receiving radioactive iodine (OT 3/10/15 issue).