Robert J. Motzer, MD:There are a number of different drugs that are acceptable and available for second- or third-line therapy. There have actually been a number of studies that resulted at the same time that compared newer treatments to everolimus, which had been the standard of care in second- and third-line therapy since around 2008. Those newer drugsnivolumab, cabozantinib, and lenvatinib/everolimus—were all compared to everolimus standard therapy, and all showed a benefit in terms of outcome.
Nivolumab showed a benefit in overall survival compared to everolimus. Cabozantinib, in both overall survival and in progression-free survival. And lenvatinib plus everolimus was compared to everolimus in a smaller randomized phase II trial but showed very robust results with regard to a high response rate, longer progression-free survival, and an increase in overall survival in the updated information.
The lenvatinib/everolimus study, a pivotal trial, was a trial that started out with a single arm lead-in with lenvatinib/everolimus to define the optimal dose and schedule for that combination. There was compelling information at the time for preclinical work that it would be very active in combination with everolimus. The suggested dose for moving forward was lenvatinib at a dose of 18 mg per day and everolimus at a dose of 5 mg per day. That was moved into this randomized phase II trial that had 3 armslenvatinib/everolimus, lenvatinib monotherapy, and everolimus monotherapy. It wasn’t originally designed for registration purposes, but the results were so compelling at the end of the trial for a benefit for lenvatinib and everolimus, that it was actually approved on the basis of that randomized phase II trial.
Transcript edited for clarity.
A Japanese-American Male With Recurrent RCC