Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU medical oncologist at the Dana Farber Cancer Institute. I'm so excited to have here with me today, a good friend and colleague, Dr. Toni Choueiri, who is a Professor of Medicine and the Chair of the GU Division at the Dana Farber Cancer Institute, as well as being the Director of the Lank Center for GU Oncology. Thank you so much for being here with me today.

Toni Choueiri: Thank you.

Alicia Morgans: Wonderful. So Dr. Choueiri, you have given us a lot of information over the years. One of the most exciting has been the KEYNOTE-564 data on adjuvant pembrolizumab in kidney cancer patients. And I would love to hear what you presented at GU ASCO 2022, about the longer term outcomes from this study. Can you tell us a little bit about it?

Toni Choueiri: Yeah. First and foremost, thank you Uro Today for always being on top of the news. And we had the chance during this meeting, which is my first meeting in two years, flying in to present six more months update of what we presented virtually at the 2021 ASCO plenary. KEYNOTE-564 was the first study to establish an immunotherapy drug, here the immune checkpoint inhibitor pembrolizumab as a standard in patient at risk of recurrence of renal cell cancer that led to the FDA approval in November 2021.

So what we presented here is six more months of follow up to see how the disease free survival holds the overall survival and to see if there's any new safety signal. And good news is the disease free survival keeps getting better. The confidence intervals are tighter from .68 to .63. Overall survival, which still only at 33% power, but still the confidence interval are getting tighter.

Good news. We don't have any new safety signals. I think it's important for patient in the adjuvant setting that get one year of pembrolizumab to see if something happens long term, longer term, which it didn't. We presented some subgroup analysis where we took out the M1-NED. We took out the patient that has T4 and N (+), so really high risk. We also looked at a patient that have T3, intermediate high. And of course we saw consistent benefit.

We also looked at the sarcomatoid, the patient with sarcomatoid feature. And while patients have a worse prognosis than not having sarcomatoid feature, the benefit of pembrolizumab was still there with or without sarcomatoid feature. So we are quite excited about these results. The hope in term of next steps are three. One is the update of the final or near final overall survival analysis. Very important. Second, some biomarker work that is in the works. And third and most important, building on pembrolizumab adjuvant, which is a new standard of care.

And we launched [inaudible], which is a randomized phase three study of pembrolizumab control versus pembrolizumab HIF-2 inhibitor belzutifan and this study hopefully will start accruing soon.

Alicia Morgans: That's fantastic. I just love that this gives an opportunity for patients who really needed something in this adjuvant setting to shift the curve. How do you have those discussions with patients? Do most patients seem really gung ho for an adjuvant treatment for a year? That's a long time, or do more patients say, "Maybe not for me?" What do those conversations look like because you shifted the curve?

Toni Choueiri: Outstanding question. We see it all. It's variable. I think we are a bit in term of medical oncologist, there is a bias here, a referral bias for which a lot of patient comes my way through a referral from the urologist. So it depends how the urologist set the tone. We work very closely with our urologists here, one team. Kudos to Dr. Adam Kibel, who leads the Division of Urology, we work very closely with. And it's a discussion. I do in practice tell the patient, I follow the eligibility criteria of keynote 564. So if someone is low risk of low grade, if someone does not have a clear cell histology, if someone had a recurrence in the lung after forty years, that was resected, I'm not sure they are even eligible for adjuvant pembrolizumab.

The other thing is, which you probably alluded on a bit, is what to do if patient get on adjuvant pembrolizumab and then experience tumor recurrence. And I think this is an unmet need in each that can develop what to do post immune checkpoint inhibitor, especially in the adjuvant setting. Of course, TKI work, should we restart immune checkpoint inhibitor? We're building some trials in that space.

Alicia Morgans: I do not doubt it. You will build a trial wherever one needs to be. And that is why we love talking to you and why your patients love you too. So what would your message be to clinicians who are thinking about this, urologists, medical oncologists? How do they make it work? What's your message in terms of adjuvant pembrolizumab?

Toni Choueiri: I think while as a GU Oncologist folks in prostate cancer have done a wonderful job with a multidisciplinary approach. In kidney cancer, we've done relatively a good job. Personally, why, because radiation was not something we talked about. Second is surgery indication was after the surgery, or even when cytoreductive nephrectomy was in question.

But now we have an opportunity also as a colleague, urologist oncologist to work together and both be part of the decision making with the patient when adjuvant therapy is indicated. So I think that's probably the largest message to our clinician. As you know, we have a very, very large practice at Dana Farber Cancer Institute, and we are happy to help in any shape or form about kidney cancer decisions. And it's a good thing for patient. I never thought during my plenary session at ASCO, I look at the first adjuvant immunotherapy study and I was in high school. It was presented at ASCO exactly 29 years earlier with interferon. And many attempts to improve immunotherapy, adding another immunotherapy, adding chemotherapy, doing vaccine studies. So it tells you that at the end of the day, there is hope even if the hope comes three decades later. Let's build on that hope.

Alicia Morgans: I love that idea. Thank you for that, Toni. And thank you for your contributions. You continue to build on the hope. We as your community, thank you, as do your patients. We appreciate your time today. Thank you again.

Toni Choueiri: Thank you.