The FDA has approved the combination of lenvatinib (Lenvima) and everolimus (Afinitor) as a treatment for patients with advanced renal cell carcinoma (RCC) following prior anti-angiogeneic therapy, based on progression-free survival  and overall survival (OS) data from a phase II study.

Lenvatinib is a 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 tumour proliferation.

There are approximately 338,000 patients with RCC across the world, with around 58,000 in the United States, 115,000 in Europe and 17,000 in Japan.

Renal cell carcinoma comprises the majority of kidney malignancies, with rising incidence in people, especially men over 50.

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.

In the trial, known as Study 205, the combination of lenvatinib and everolimus reduced the risk of progression or death by 63% compared with the mTOR inhibitor everolimus alone.

Study 205 was a multicenter, randomised, open-label study of the combination of lenvatinib (18 mg) plus everolimus (5 mg), Lenvima 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 randomised 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 Lenvima 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 Lenvima 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 Lenvima alone group was 7.4 months, demonstrating an extension in PFS compared to the everolimus alone group (HR: 0.61 [95% CI: 0.38-0.98]).

Prior to the approval, the combination of lenvatinib and everolimus had received a breakthrough therapy designation as a treatment for RCC.

The combination was approved earlier than anticipated, under the FDA's priority review program.

Source: FDA Approved Drugs