Second-Line Therapy Following a TKI/IO Regimen for Favorable-Risk RCC

A brief discussion on available treatment options after patients progress following frontline TKI/IO therapy with favorable-risk renal cell carcinoma.


Robert J. Motzer, MD: The last question on this case, I’ll direct it to Brian. For this patient, assuming that perhaps they have progression in less than 6 months, what is your approach to patients who are progressing on lenvatinib and pembrolizumab in relatively short order after an initial response?

Brian I. Rini, MD: I think, whether their response is long or short, I’m not sure it’d be different. I tend to use cabozantinib second. I think it’s the most active drug that such a patient would not have seen yet. As you’re aware, we don’t yet have level 1 evidence for using immune therapy in sequence, although there are trials ongoing, so I don’t do that off protocol. I tend to give a single-agent TKI [tyrosine kinase inhibitor], realizing that it’s fairly unexciting, but I think that is the default standard, and I tend to give cabozantinib. Unless for some reason, I gave cabozantinib and nivolumab up front, then of course I’d pick a different TKI, but I tend to use the pembrolizumab-based doublets that we’ve talked about.

Robert J. Motzer, MD: Thanks. Just one last question, if this patient had been treated with axitinib plus pembrolizumab and progressed, so they never had a response to axitinib plus pembrolizumab, or a very brief response, Bob, what would you go to next in that sort of a patient?

Robert S. Alter, MD: I know there are still no level 1 data, but people have started talking about giving ipilimumab plus nivolumab a bit. I agree with Brian, I think cabozantinib seems to be a very good second-line agent. Yes, at the same time too, based upon the data from len/eve [lenvatinib and everolimus], it seems to be very good in regard to a second-line regimen. We’ve seen dramatic responses, progression-free survival data, and durability. Tolerability seems to be a bit of a concern, but adjusting the doses as we have just discussed seems to be very appropriate. And again, you do get exposure to an mTOR [inhibitor] that we have not seen before, so sometimes giving a different mechanism may offer a better response in patients who failed IO [immunotherapy]/TKI therapy.

Robert J. Motzer, MD: Thanks very much for that insight. I think it’s a great case and a great discussion.

Transcript edited for clarity.

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