Dr. Agarwal on the Combination of Lenvatinib and Everolimus in mRCC

Neeraj Agarwal, MD, associate professor, Division of Oncology, Department of Medicine, University of Utah School of Medicine, Huntsman Cancer Institute, discusses the combination of lenvatinib (Lenvima) and everolimus in the treatment of patients with metastatic renal cell carcinoma (mRCC).

In 2016, the FDA approved the combination of lenvatinib and everolimus for patients with mRCC based on positive data from a phase II trial. In the 3-arm trial, investigators compared the use of lenvatinib with that of everolimus and of lenvatinib plus everolimus, explains Agarwal. There were 50 patients in each arm. Results showed that lenvatinib was not superior to everolimus in terms of progression-free survival (PFS), which was the primary endpoint of the study. The FDA approval was based on the combination’s superiority over everolimus alone, says Agarwal.

The study demonstrated improved efficacy with the combination, resulting in a median PFS of 12 to 13 months versus 4 to 5 months with everolimus monotherapy. However, the regimen is associated with added toxicity and cost. Therefore, for frail patients who progress on first-line therapy, Agarwal recommends cabozantinib (Cabometyx) as the next line of therapy. When those patients progress on cabozantinib, the combination of lenvatinib and everolimus can be introduced, he concludes.