Lenvatinib mesylate ( Lenvima ) is an orally administered multiple receptor tyrosine kinase ( RTK ) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor ( VEGF ) receptors ( VEGFR1, VEGFR2 and VEGFR3 ) and fibroblast growth factor ( FGF ) receptors ( FGFR1, FGFR2, FGFR3 and FGFR4 ) in addition to other proangiogenic and oncogenic pathway-related RTKs ( including the platelet-derived growth factor [ PDGF ] receptor PDGFRalpha; KIT; and RET ) involved in tumor proliferation.
Lenvima is now also approved for an additional indication in the United States in combination with Everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy.
A new drug application seeking approval for an indication covering advanced or metastatic renal cell carcinoma submitted in Europe in January 2016 is under review.
Eisai is conducting clinical studies of Lenvima in several other tumor types such as hepatocellular carcinoma ( phase III ), endometrial carcinoma ( phase II ), biliary tract cancer ( phase II ), and in combination with an immune checkpoint inhibitor ( phase Ib/II ).
Study 205 was a multicenter, randomized, open-label study of the combination of Lenvatinib ( 18 mg ) plus Everolimus ( 5 mg ), Lenvatinib alone ( 24 mg ), and Everolimus alone ( 10 mg ) in patients with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy, and was conducted in Europe and the United States.
153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the efficacy and safety of these three regimens.
From the results of the study, the combination of Lenvatinib plus Everolimus group demonstrated a significant extension in the study's primary endpoint of progression free survival ( PFS ) compared to the Everolimus alone group ( median PFS for the Lenvatinib plus Everolimus group: 14.6 months vs median PFS for the Everolimus alone group: 5.5 months; hazard ratio ( HR ) 0.40 [ 95% CI: 0.24-0.68 ], p=0.0005 ).
Additionally, median PFS for the Lenvatinib alone group was 7.4 months, demonstrating an extension in progression-free survival compared to the Everolimus alone group ( HR: 0.61 [ 95% CI: 0.38-0.98 ] ).
The study also assessed objective response rate ( ORR ) and overall survival ( OS ) as secondary endpoints. Regarding ORR, both the Lenvatinib plus Everolimus group and the Lenvatinib alone group showed an improvement in ORR compared to the Everolimus alone group (Lenvatinib plus Everolimus: 43%, Lenvatinib alone: 27%, Everolimus alone: 6% ).
Furthermore, regarding overall survival, an updated analysis carried out in December 2014 suggested that Lenvatinib plus Everolimus extends overall survival compared to Everolimus alone ( HR: 0.51 [ 95% CI=0.30-0.88 ] ).
The most common treatment-emergent adverse events ( TEAEs ) reported in the Lenvatinib plus Everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of grade 3 or higher were diarrhea, hypertension and fatigue.
The number of patients with renal cancer was estimated to be approximately 338,000 worldwide, including approximately 58,000 in the United States, 115,000 in Europe and 17,000 in Japan.
Renal cell carcinoma comprises more than 90% of all malignancies of the kidney, and occurs when malignant cells are found in the lining of the tubules of the kidney.
The incidence of renal cell carcinoma in people aged in their late 50s is rising, and is more likely to affect men than women.
For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment method is molecular targeted drug therapy, however with low 5-year survival rates, this is a disease with significant unmet medical need. ( Xagena )
Source: Eisai, 2016