Cabozantinib + Nivolumab Regimen in the Treatment of Advanced RCC

Robert Alter, MD: Earlier, I mentioned why I use cabozantinib-nivolumab. We had to utilize an IO [immunotherapy]/TKI [tyrosine kinase inhibitor], as Elan mentioned before. At what point do you realize you have to bring out more aggressive therapies? IO/IO would’ve been well tolerated in someone with brain metastases, so that would have been fine. I felt that he was having more symptomatic disease and that we had to become a lot more cognizant of symptom improvement in a shorter period of time. Of the 3 IO/TKI regimens that we commonly use, we believe it has an impact in improvement in function and performance status about 3 weeks quicker than IO/IO. But I definitely believe that when you have to utilize symptom relief much faster in someone who’s eligible to receive a TKI therapy, that’s something we have to be aware of. Despite the fact that we have many options, we have to come up with our core foundation about the solution.

With bone metastases, we always think that cabozantinib is the right drug, although it isn’t perfect with everyone with bone metastases. Ten years ago, a drug called XL184, which was being studied for prostate cancer, made bone lesions disappear. That was cabozantinib in its infancy. It isn’t FDA approved for prostate cancer, but this is something we’ve always felt that the bone lesions can respond well to. What are your thoughts on cabozantinib-nivolumab? You must have used it. How do you find the tolerability? Where do you find the ideal patient in your settings?

Elan Diamond, MD: I agree with you 100%. I select patients with bone and brain metastases to treat with cabozantinib-nivolumab. In my experience, it’s a fairly well-tolerated regimen. It’s a little better tolerated than lenvatinib-pembrolizumab. The adverse reactions are fairly similar but less severe. But if you look at the CheckMate 9ER data, 56% of patients required dose reductions in that study. But I’d use it in the exact same way you have.

Robert Alter, MD: As you had in your first case, your patient was on maintenance therapy before he had to come off, and I have my gentleman on maintenance therapy at this point. I don’t know which drug to stop. Is it wrong to stop any of them? The patient has been enduring therapy well. I can’t tell you which drug made the most success. He’s tolerating the combination well. At this juncture, my approach isn’t to stop his therapy. He hasn’t had a clear toxicity to [either drug] that makes me feel we have to [stop].

All of our patients present differently when it comes down to it. You have to have these conversations with the patients. There are patients who come in and hear what they think they hear. Let’s say you give them IO/IO, 4 cycles of ipilimumab-nivolumab. You say, “We’ll do the scan afterward.” You do the scan, and they say “OK, am I done?” You say, “No, now we have more,” but they don’t hear everything. You have to always discuss the goals of care and the plan with your patients. The reinforcement helps them a little. Some patients get it and some patients can’t wait.

Then we have to have a conversation with some patients who wish to stop therapy. Do you stop one drug? Which drug do you stop? I don’t have enough experience to tell you that it’s easy to stop one. If they have TKI toxicity, that’s very easy. I’d stop that. If you have any concerns that they’re living far away and can’t come in as often, then stopping the IV [intravenous] therapy may be beneficial. But we’re going to see this over the course of many years, and we have to talk to our patients about how we have to adjust our therapies, our management.

Elan Diamond, MD: I agree 100%. Maybe the best guidance with this would be the pembrolizumab-axitinib data from KEYNOTE-426 where they continued the pembrolizumab for 2 years and then stopped it and just continued the TKI. They had a lot of patients with sustained response who did well after that. That’s the best level 1 evidence that I’m aware of regarding what to stop. But you’re correct, these are major clinical problems that need to be answered.

Transcript edited for clarity.