New Combination Therapy for Treating Advanced RCC Receives FDA Priority Review

A new combination therapy for treating advanced renal cell carcinoma (RCC) is showing promise in early clinical testing and may soon be approved the US Food and Drug Administration (FDA). 

On January 17, 2016, The FDA accepted for Priority Review the supplemental New Drug Application for lenvatinib (Lenvima) for the potential treatment of patients with unresectable advanced or metastatic RCC in combination with everolimus (Afinitor) following one prior vascular endothelial growth factor (VEGF)-targeted therapy.

The FDA had previously granted lenvatinib Breakthrough Therapy Designation for this investigational indication. Lenvatinib, discovered and developed by Eisai Inc., is a multiple receptor tyrosine kinase inhibitor.  Currently, it is sold under the name Lenvima and it is approved for treating patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory, differentiated thyroid cancer (DTC).

"With the FDA's acceptance of this supplemental application, we are one step closer to potentially providing the first tyrosine kinase and mTOR inhibitor combination therapy to patients with unresectable advanced or metastatic renal cell carcinoma," said Kenichi Nomoto, PhD, President, Oncology Product Creation Unit, Eisai Product Creation Systems, in an Eisai press release. "We look forward to working with the FDA over the coming months as it considers this potential new option for patients with advanced RCC."

The announcement from the FDA comes on the heels of the latest progression-free survival (PFS) data from a three-arm, phase II study comparing lenvatinib in combination with everolimus, everolimus alone, and lenvatinib alone in RCC patients.

In this study, there were 153 patients enrolled and 99% had one prior VEGF-targeted therapy.  Researchers reported that lenvatinib plus everolimus prolonged PFS compared to everolimus alone (hazard ratio 0.40). The combination therapy also improved the objective response rate (ORR) compared to everolimus alone. The study showed that the median duration of response was longest in the arm receiving lenvatinib plus everolimus (13.1 months). For the lenvatinib alone arm, the duration of response was 7.5 months and for the everolimus alone arm it was 8.5 months. The researchers found lenvatinib plus everolimus appeared to be superior to everolimus alone in an analysis of overall survival (OS).

In this investigation, the most common treatment-related adverse events were hypertension (73%), diarrhea (67%), decreased appetite (54%), myalgia (62%), and fatigue (67%) in patients receiving lenvatinib plus everolimus.

Lenvatinib inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. It also inhibits other receptor tyrosine kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions.