Study 205 is a multicenter, randomized, open-label study of Lenvatinib ( 18 mg ) in combination with the anticancer agent Everolimus ( 5 mg ), Lenvatinib alone ( 24 mg ), and Everolimus alone ( 10 mg ) in patients with advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy.
153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the safety and efficacy of these three regimens.
From the results of the study, the combination of Lenvatinib plus Everolimus demonstrated a significant extension in the study's primary endpoint of progression free survival ( PFS ) compared to Everolimus alone ( 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 less than 0.001 ).
Additionally, median PFS for Lenvatinib alone was 7.4 months, demonstrating an extension in progression-free survival compared to Everolimus alone ( 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 overall response rate ( 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 ( OS ), 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 ( TEAE ) reported in the Lenvatinib plus Everolimus group were diarrhea, decreased appetite and fatigue.
The most common TEAEs of grade 3 or higher ( Common Terminology Criteria for Adverse Events ) included diarrhea, hypertension and fatigue.
Lenvatinib ( 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 PDGFR-alpha; KIT; and RET ) involved in tumor proliferation.
Lenvatinib has been confirmed through X-ray co-crystal structural analysis to demonstrate a new binding mode ( type V ) to VEGFR2, and exhibits rapid binding to the target molecule and potent inhibition of kinase activity, according to kinetic analysis.
Currently, Lenvatinib is indicated for the treatment of refractory thyroid cancer. Eisai is conducting a global phase III study of Lenvatinib in hepatocellular carcinoma as well as phase II studies of Lenvatinib in several other tumor types such as endometrial carcinoma and non-small cell lung cancer.
The number of patients with renal cancer was estimated to be approximately 338,000 worldwide, including approximately 17,000 in Japan, 58,000 in the United States and 115,000 in Europe.
Renal cell carcinoma comprises more than 90% of all malignancies 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.
Source: Eisai, 2015