Benjamin Garmezy, MD: The most recent patient that I can think about in clinic got pembrolizumab-lenvatinib. Younger patient; healthier patient. Our patient’s a little bit on the older side from what I just presented, but let’s say we started pembrolizumab-lenvatinib, and then let’s use that as a segue to discuss. Dr Barata, what percentage of your patients move on from front line to second line in your own clinical experience?

Pedro Barata, MD, MSc: That’s a great question. The answer depends on how long you’re treating them. We’re assuming we start today; 10 patients on an IO [immuno-oncology]–TKI [tyrosine kinase inhibitor], and then you’re going to check back in 2 or 3 years, right? To get an idea of the numbers, we expect progression in half of our patient population between a year and a half to about 2 years. That’s what I’ve seen in clinic; so, it’s fairly common. I have patients on an IO-based approach who stay on treatment beyond [the] 1-year mark, and a few patients who remain on therapy, or without progression, longer than 2 years.

My observations from my practice are not different from what the data have reported. I start expecting progressions within a year and a half to 2 years, but I have these durable responders, patients where I have the question about 2 years later. I’m debating with them whether we should be stopping the IO and go on a watchful waiting approach. For some of them, I go a little bit beyond 2 years if I see disease and I know for a fact there is disease, it shrank, but it’s not a complete CR or a near CR. I’ve stopped therapy for some patients in whom I’ve seen very close to complete response, and I have a couple of patients who have been doing well on watching. These data seem to be concordant to what I’m seeing in real life. Dr Garmezy, is that your experience? What happens when patients end up progressing?

Benjamin Garmezy, MD: Yes, that echoes my experience. Then the question is, what do you do next? Let’s say this patient got pembrolizumab-lenvatinib, then the second line would be a single-agent TKI as far as our current NCCN guidelines suggest. Cabozantinib has a lot of data in the second line. It’s a tried-and-true workhorse for our community oncologists across the country. We now have data with CaboPoint, which was further cemented and presented at ASCO GU 2023 [American Society of Clinical Oncology Genitourinary Cancers Symposium] only a week ago, suggesting that it has reasonable response rates in the subsequent line setting.

Generally with cabozantinib, if I haven’t used it in the front line with that data set, with cabozantinib-nivolumab, then I’m going to use it in the second line if I haven’t used it before. If I used cabozantinib-nivolumab in the front line—let’s say I gave that instead of pembrolizumab-lenvatinib because I was concerned about the dose of the lenvatinib in that frontline setting—then you can’t use cabozantinib in the second line. Then what do you do? You have options for either axitinib or a combination with lenvatinib and everolimus, which is a doublet therapy with mTOR inhibition added to that VEGF-TKI. It’s more toxic in that combination than a single-agent TKI, so I go from there.

As far as the other question that I get from my referring doctors in the community and the doctors within my practice who like to discuss emerging data, should we be continuing immunotherapy? The question needs to be answered and will be answered. We have 2 data sets right now, 2 large phase 3 trials that are going to help us provide that answer. As far as your practice, Dr Barata, if that patient got pembrolizumab-lenvatinib, what would be your next step? And what would change if that patient got ipilimumab-nivolumab instead?

Pedro Barata, MD, MSc: I like that you highlighted CaboPoint. We traditionally quote a few data sets to support our decision [in a] refractory setting, so we think about METEOR for cabozantinib, and now CaboPoint favors cabozantinib. We have the data with lenvatinib and everolimus combination, which is a phase 2/3 cohort. It is true that many patients who got IO in the frontline. There’s a limitation there.

Another option is the tivozanib, based on TIVO-3 data. Before I put you on the spot regarding the TIVO-3 data, for a patient, I agree with you that it matters what you get in the frontline space to decide what you’re going to get upon progression. For the most part, if I have a patient who hasn’t seen a TKI or has seen a TKI that’s not cabozantinib, cabozantinib will likely be my default plan. In addition to cabozantinib, lenvatinib, everolimus, and tivozanib, I should also highlight axitinib. If I have a patient who was treated with ipilimumab-nivolumab, even cabozantinib-nivolumab, axitinib should be a part of the treatment options available in the refractory setting. I might consider those agents. And if I have a patient who is treated with lenvatinib-pembrolizumab, then I’m going to debate whether I do cabozantinib, tivozanib, or sunitinib.

Transcript edited for clarity.