Are Combinations the Answer in Metastatic RCC? - Episode 3

Dosing Strategies to Maximize Efficacy in RCC

Robert J. Motzer, MD, discusses dosing strategies to mediate toxicities and maximize efficacy from the frontline combination of lenvatinib plus pembrolizumab for renal cell carcinoma.

Robert J. Motzer, MD: Lenvatinib in the combination with pembrolizumab is given at a relatively high dose. The dose of lenvatinib is 20 mg per day, given with pembrolizumab at standard dosing every 3 weeks. For the most part, the strategy with lenvatinib combination therapy and monotherapy in RCC [renal cell carcinoma] and other malignancies has been to start with a high dose, with the concept that that efficacy is increased or maximized by giving higher doses or adequate therapeutic doses of lenvatinib, then to manage toxicity with supportive care measures, as well as dose modification as needed. Initially, to start with a high dose for a purpose of maximizing efficacy, then modifying dose and providing supportive care measures as needed for patients experiencing adverse events. For the lenvatinib-pembrolizumab combination program, just about all the patients had a treatment-related adverse event, and 72% had a grade 3 or higher treatment-related adverse event. The dose modifications of lenvatinib are common as I mentioned, and in this particular trial with this program, 67% of patients, or about two-thirds of patients, required a dose modification. This is typical with lenvatinib combination therapy. I will say, however, that the median duration of treatment for lenvatinib plus pembrolizumab was 17 months, compared with only 7.8 months with sunitinib. Although there are a fair number of adverse events and treatment modifications, the median duration of therapy was 2.5 times the length of lenvatinib plus pembrolizumab, compared with sunitinib, which is certainly an important factor. Less than 20% of patients, however, required dose discontinuation of lenvatinib. Meaning that in most cases, the toxicities were managed successfully by dose modification and by supportive care measures. Less than 10% of patients had dosed discontinuation of the lenvatinib and the pembrolizumab because of toxicities on the trial.

Transcript edited for clarity.