On May 13, the Food and Drug Administration (FDA) approved a new oral combination therapy for patients with advanced renal cell carcinoma (RCC), the most common kidney cancer in adults.
This combination therapy involves taking capsules of lenvatinib and everolimus on a daily basis. Both drugs are signal transduction inhibitors that stop some of the signals within cells that make them grow and divide. Lenvatinib (brand name Lenvima) works by inhibiting vascular endothelial growth factor (VEGF) receptors, halting blood vessel formation (angiogenesis) and fibroblast growth factor (FGF) receptors. FGF receptors are thought to be responsible for the development of cancer progression (treatment-resistance) following other anti-VEGF therapies. Levantinib was first FDA-approved in 2015 to treat some forms of recurrent and metastatic thyroid cancer. Everolimus stops a particular protein called mTOR from working which helps stop cancer growth. Everolimus was the first mTOR inhibitor approved in 2009 for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.
This treatment regimen is only FDA-approved as a second-line treatment for those who have already undergone one prior anti-angiogenic therapy. Common anti-angiogenic therapies for metastatic kidney cancer include sunitinib and pazopanib. Rather than targeting the tumor cells directly, anti-angiogenic therapies aim to prevent the growth of blood vessels the tumors depend on for survival.
Dr. Ana Molina of the Weill Cornell Medicine Genitourinary Oncology team led the initial study that tested this combined treatment which demonstrated that the regimen was not only safe, but showed impressive enough anti-cancer activity to warrant a larger, multi-center, randomized trial.
In the randomized trial that ultimately led to FDA-approval, patients who received lenvatinib and everolimus had significant improvement in progression-free survival (PFS) of 14.6 months versus 5.5 months with only everolimus. The overall response rate was 43% with the combination, compared with 27% with Lenvatinib alone and 6% with everolimus. The median overall survival was 25.5 months for the combination arm, 19.1 months in the Lenvatinib monotherapy arm and 15.4 months in the everolimus arm. Side effects included diarrhea, fatigue, high blood pressure (hypertension), nausea and vomiting, weight loss and protein in the urine.
We continue to offer lenvatinib and everolimus as combination therapy and encourage you to ask about whether it would a good treatment course for you.