Robert J. Motzer, MD:I participated in the phase I study, and in the randomized phase II trial, and in studies afterwards with lenvatinib and everolimus. Including the pivotal phase III trial that’s ongoing, with lenvatinib/everolimus, compared to lenvatinib/pembrolizumab, compared to sunitinib in first-line treatmenta nearly 800-patient trial referred to as the Clear Cell trial, to investigate the lenvatinib/everolimus regimen, and lenvatinib/pembrolizumab in first-line therapy.
As part of standard management and in the earlier studies, my experience with lenvatinib/everolimus has been very favorable, particularly with regard to its efficacy. There’s certainly safety aspects associated with that, with a frequent dose reduction. Most patients do experience an adverse event of one type or another, but I felt that overall, the adverse events are manageable, and I have been very impressed by the efficacy for the regimen.
Lenvatinib is a typical tyrosine kinase inhibitor, and its predominant side effects include hypertension. It can cause diarrhea; it can cause skin toxicity. One of the adverse events that we see that are higher with lenvatinib compared with some of the other TKIs like sunitinib and pazopanib, is proteinuria as well. So, those are important to monitor in patients treated with lenvatinib.
Everolimus, a very well tolerated drug, adds little to the toxicity. The main side effects with everolimus are stomatitis and also, it can rarely cause pneumonitis. So, in the combination of lenvatinib/everolimus, overall it was pretty well tolerated for patients in the phase II trial, although frequent dose reductions were required. In that study, about 60% of patients required a dose reduction, which was generally of the lenvatinib.
Oftentimes, toxicity is seen with that particular regimen, but one of the philosophies of that regimen is to start out with full dose, anticipating that many patients will require a dose reduction. The dose reductions are most common for hypertension, diarrhea, or the proteinuria.
Transcript edited for clarity.
A Japanese-American Male With Recurrent RCC