Frontline Treatment for mRCC: Dose Adjustments/Discontinuation


Advice for appropriately dosing newer novel-based strategies used to treat metastatic renal cell carcinoma and best practices to help community oncologists avoid drug discontinuations.

Sumanta Kumar Pal, MD: Tom, I saw you nodding. Let’s talk about the issue of discontinuations being a good metric of quality of life. You were telling us how great lenvatinib-pembrolizumab is, but my recollection is that it has the highest rate of dose reductions and treatment discontinuations. How about that?

Thomas E. Hutson, DO, PharmD: I don’t know that the number of discontinuations was the highest, but the number of dose reductions was up there around cabozantinib. We talk about how those newer-generation agents, along with great efficacy, have a more robust adverse-effect profile. You can continue to keep people on therapy by being conscious of that and dose reducing. I like to see in a drug that dose reduction allows patients to stay on therapy and achieve the benefit in a low discontinuation rate. If I recall, the discontinuation rates with all the TKIs [tyrosine kinase inhibitors] are pretty low. You have a much higher dose-reduction rate than you have the discontinuation rate, suggesting that you are able to individualize and find that happy medium dose for patients. To me, that’s more practical. I agree with Dave. It’s a more practical and meaningful end point than getting a health-related quality of life, which has a lot of intrinsic bias within it.

Robert S. Alter, MD: I spoke to Eric Jonasch years ago about how we dose suggest around sunitinib sometimes 10 days on, 4 days off. In the trenches, in the clinics, or in the community, we have to make sure that if we have a tolerable therapy that becomes intolerable, but it’s a therapy that’s effective, we have to try to make it more tolerable. We definitely dose reduce more. I have a few patients who are taking lenvatinib at 4 mg per day or 4 mg every other day as a fantastic therapy. Their quality of life is amazing, and the disease is not growing. When you don’t have patients on clinical trials, how much lower can we go to make sure that our patients are not having drug discontinuation? It’s an exception when we have patients this low, but this goes down to the fact that we still believe that VEGF inhibition needs to be continued in some these patients. The dose adjustments have to be based on the patients’ quality of life, not just the data.


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