I/O–I/O Therapy in Intermediate/Poor Risk RCC: Toxicity and Duration of Response


Focusing on immunotherapy in the setting of intermediate- and poor-risk renal cell carcinoma, panelists review toxicity management and duration of response.


Robert J. Motzer, MD: One characteristic aspect of the ipilimumab-nivolumab program that you spoke to earlier was I/O [immuno-oncology] toxicity. The experience has been that the I/O toxicity tends to occur earlier during the course of ipilimumab, but after that there’s the time period when patients are getting monotherapy with nivolumab. My experience has been that they have a good quality of life. Usually, there are fewer of the chronic toxicities that we see with the TKI [tyrosine kinase inhibitor]–I/O combinations, which is a strong point in favor of ipilimumab-nivolumab: the quality of life long term with these patients. The other point that’s come up is the durability of response. What’s been your experience, Maria, in terms of durability of response or the data for durability of response with ipilimumab-nivolumab?

Maria I. Carlo, MD: With each presentation of the data long term, it does seem that there’s that curve of patients who are still progression-free. I have a few patients who are no therapy who got ipilimumab-nivolumab many years ago. A lot of them developed a toxicity and then had to come off, but their disease hasn’t recurred necessarily. In my patient population, I can see the tail of the curve of patients who are still disease-free many years later on or off maintenance therapy. What about patients who want to remain on maintenance therapy? We don’t know the utility of keeping somebody on nivolumab long term, for example, but that’s how this original trial was designed. Some patients don’t want to bother with the infusions, but some don’t want to come off the infusions because they know it’s working for them.

Robert J. Motzer, MD: Dr Lee, I recall that you were recently a coauthor on a paper who looked at treatment-free interval for patients treated with ipilimumab-nivolumab. One question comes up: if a patient has an I/O–related toxicity, do you think that’s a good thing? Does that correlate with response or outcome? Do those patients have favorable outcomes?

Chung-Han Lee, MD: Based on the original trial design for CheckMate 214, for people who had significant I/O toxicities, it was a protocol-mandated discontinuation of the I/O therapy. In clinical practice, some people have taken people who were on ipilimumab-nivolumab and rolled them into maintenance therapy. However, that was not an option in the CheckMate 214 study. That provided the opportunity for analysis of CheckMate 214 for patients who develop I/O toxicity, to look at their outcomes and whether they could have a significant treatment-free interval. That study showed that if you came off for toxicity, there was a significant proportion of patients who remain treatment-free and may not have needed subsequent therapy. One thing I do express to patients, especially if they develop toxicities, is that even though they’re discouraged if they develop an I/O toxicity, there’s the possibility that this may be an indication that they may respond quite well and may not need subsequent therapy down the line. We focus on getting through the immediate event with hopes that things will subsequently get significantly better.

Transcript edited for clarity.

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