Are Combinations the Answer in Metastatic RCC? - Episode 4
Expert perspectives on the clinical utility of lenvatinib plus pembrolizumab as a frontline combination for advanced renal cell carcinoma.
Robert J. Motzer, MD: With regard to personal experience for lenvatinib, I have been involved with lenvatinib clinical trials in kidney cancer for more than 10 years. I led the original trial, which was a dose-finding trial for lenvatinib plus everolimus, that established the dose for that particular combination, and for the randomized phase 2, which compared lenvatinib everolimus and lenvatinib monotherapy with sunitinib. That study resulted in regulatory approval for that combination in second-line therapy. I was also a key investigator in the initial dose-finding study for lenvatinib plus pembrolizumab, across multiple malignancies, and for the dose expansion in renal cell cancer that has totaled more than 140 patients.
I was also the principal investigator for the CLEAR trial, and I personally treated close to 40 patients on that trial at my center. I’ve had considerable experience with lenvatinib combination therapy and with lenvatinib-pembrolizumab. I find that it is a very effective regimen in terms of producing response and clinical benefit. I like the plan of starting with a with a high therapeutic dose of 20 mg lenvatinib-pembrolizumab or 18 mg lenvatinib-everolimus and then dose-reducing as needed for adverse events that patients develop. For the most part, these adverse events seem to occur over the course of treatment for the patient. They don’t happen within the first 2 months or so; it seems to be over the course of the patient’s treatment. There really are multiple causes for the dose reduction. Sometimes it could be hypertension, sometimes proteinuria. It’s really mixed—occasionally it’s fatigue or stomatitis. There doesn’t seem to be 1 adverse event that dominates, that results in the majority of the dose modification, so it seems like a mixed picture. Very often, patients start at 20 mg, or if lenvatinib-everolimus, at 18 mg. On long-term treatment, they are comfortable on the 10-mg dose of lenvatinib and are able to maintain that dose for a long time. So the more hands-on experience physicians get with lenvatinib in combination with pembrolizumab, the more comfortable they will be in terms of using this tyrosine kinase inhibitor in a way that maximally benefits their patients.
Transcript edited for clarity.