Selecting RCC Patients with Lenvatinib + Pembrolizumab Therapy and Appropriate Dosing Strategies

Shawnta Anakwah, MD: Can you please describe your decision-making process and how you chose lenvatinib plus pembrolizumab for this particular patient?

Arnab Basu, MD: This is a good question. The data suggest that almost all these other regimens are very effective in controlling disease with high overall response rates. Although one shouldn’t be comparing across trials, pembrolizumab plus lenvatinib appears to have the highest overall response rate, which is why I tend to choose this regimen for high disease volume or a particularly aggressive course that needs disease control immediately. In patients who have a lot of bony disease involvement, the activity of cabozantinib has been historically very good and is supported by the CheckMate 9ER trial. I prefer to use that regimen in patients with bony predominant disease. And finally, pembrolizumab and axitinib is overall a very well-tolerated regimen with excellent follow-up data. Indeed, it has the longest follow-up among all the IO [immunotherapy]/VEGF combinations because it was the earliest to come up with the data. Further, axitinib allows the most flexibility in dose titration as it’s available in a 1-mg pill. And I do prefer using that in patients who are relatively frail and need a gentle uptitration in their regimen.

Shawnta Anakwah, MD: Dr Basu, can you please tell us about your experience with lenvatinib and pembrolizumab, toxicity wise, and your experience with your practice?

Arnab Basu, MD: Thank you for the question. I use a lot of lenvatinib and pembrolizumab in the front line, and in fact, even in a refractory setting, based on the refractory CheckMate data. In the front line setting, patients are more robust. Depending on the patient, if they would be able to go on a phase 3 trial, for example, I would put them on a 20-mg lenvatinib dose with pembrolizumab. The challenge is that in the CLEAR study, the first dose reduction on pembrolizumab is from 20 mg down to 14 mg. However, I know this is off-label, but I have seen some of the frailer patients sometimes do OK on 18 mg, and then I can sometimes go up to 30 mg. The question is, how long are we able to maintain dose density and duration for TKIs [tyrosine kinase inhibitors] in some of these studies? In almost all the patients, I would try to get them onto 20 mg, but occasionally, I would use a lower dose, and that could be 18 or 40 mg depending on guidelines that you would like to follow.

In terms of adverse effects, I have seen a lot of hypertension from this regimen. The stomatitis has, again, popped up occasionally. But overall, this is a well-tolerated regimen. Some immune toxicities occur, but not more than expected with the other IO/TKI combinations. Even though, it seems like a high dose up front, in my experience, it has generally been well tolerated.

Transcript edited for clarity.