Chapters Transcript Video 2022 GU ASCO Kidney Cancer Highlights Back to Symposium Kidney Cancer Highlights featuring Vincent Xu, MD and Toni Choueiri, MD if you're just joining us, welcome to the geo oncology conference highlights focus on ask ogu 2022 we'll be starting with kidney cancer highlights presented by dr Vincent shoe um with Tony sherry as a discuss isn't. Um Just a quick comment. Please put any questions during the presentation in the chat and we'll have time for discussion at the end and so without further ado Vincent. Do you want to? I will advance slides as needed. Thanks jake. Um So I will start by this From Keno 564 which is the adjuvant trial that investigated embolism ob after affected me for patients with high risk localized renal cell carcinoma. Now this data was first presented last year and public the new England Journal of Medicine And after you ask, oh this is the updated 30-month data cut off. Um For both the FS and for Os. So as we know kino 564 compared placebo versus federalism math. In patients with high risk localized RCC status post resection and it established a role for adjournment embolism map in clear cell RCC leading to as well the FDA approval for a drink paperless a mob for this indication. Three months ago Previously, months of data were presented and this update includes an additional six months of data with the data cut off of june 2021 As context. I think it's important to keep in mind the eligibility criteria for keynote 564. This included histological confirmed clear cell renal cell carcinoma that was intermediate high risk high risk or also patients who were M. One N. E. D. Meaning that they had metastatic optical metastatic disease at time of presentation which was completely respected within one year of an effect on me. Patients were required to have gone no prior systemic therapy And were randomized 1-1. And the primary endpoints for disease free survival as assessed per investigator as well as overall survival was a key secondary endpoint alright next life. So the keynote 564 update showed that disease free survival benefit was maintained well at 30 months with the curves remaining quite separate with additional six months of data and with a stable hazard ratio strongly favoring Federalism map over placebo has a racial remains at 0.63 And the nominal p value remains at less than 0.0001. Um As you recall previously reported including in the new England Journal paper from last year It was a hazard ratio of 0.68. And so this hazard ratio has stable, remain stable and in fact improved a little bit with the new data. In addition the disease free survival benefit was seen in the intermediate high risk the high risk and the M. One N. E. D. Sub groups and in all three groups there is clear difference between embolism map and placebo and the confidence intervals continue to favor populism map in all groups although because of the lower number of patients with only About 40 patients per arm and the high risk group, The confidence interval does cross one next slide. So subset analyses continue also to show benefit of embolism map. In all subgroups, with every subgroup favoring embolism map over placebo. Of note, this includes patients with both high grade and low grade tumors, although patients with sarcoma toy features what we might consider. The patients with the highest grade tumors um appeared to have especially large magnitude of benefit with the hazard ratio of about 0.54. So my takeaway from these substance analysis by grade is that patients with low grade tumors still appear to have some benefit from liberalism math, certainly the hazard ratio favoring that over placebo, but with each successive increase in our grade, there appears to be greater magnitude of absolute benefit. Again, of course, the subgroups, the confidence intervals cross and this is just have a little similarly benefit was seen favoring Federalism map regardless of whether Pd L one status was positive or negative. So again, with wide confidence intervals given the relatively low number of patients next please. In addition, after overall survival data was presented and there is an ongoing trend towards improved overall survival among patients who were randomized to Pemberley Elizabeth. The number of events remains low, with only 23 events on temporal is a map at 43 events on Placebo. And so the survival data is still not considered mature. The hazard ratio for overall survival was 0.52 Favoring Liberalism map with a P value of 0.0048. And despite this low p value because the number of events is not considered statistically mature, the P value does not yet cross the pre specified boundary for statistical significance, which for this analysis is a very strict boundary of 0.95. Um so technically not reaching the pre specified overall survival endpoint yet, but certainly trending in the right direction. Mm hmm. So in conclusion, updated data from keynote 564 showed us that achievement Embolism map continues to maintain clinical benefit at 30 months. Follow up with ongoing separation of DFS and OS curves and a strong trend towards superior Os. Though not yet reaching statistical significance. There were no new or unexpected safety signals. Scene As you recall, temporal is a map was associated with 20 points far chances of requiring systemic steroids and that safety signal was maintained. And this data shows us that embolism ab remains a standard of care for M zero or M one Ntd patients who are at high risk of recurrence from clear cell kidney cancer after surgery. So next, I'll discuss an abstract which presented the first data from neo adjuvant available in patients with localized renal cell carcinoma after, who had high risk of recurrence after an appendectomy. So in the peri operative space, but we know south carcinoma, there is FDA approval for most recently Embolism after and previous to that soon it nipped in the adjuvant space. But no approvals in the neo adjuvant space. And in the past peri operative trials have predominantly focused on achievement as opposed to theological treatment. So that being said the role of neo adjuvant therapy in general and especially of neo adjuvant IOT K. I therapy is not known in clear cell kidney cancer. Um The prior neo a german data has been really um in the modern era relegated to phase two trials and the data has been mixed. So Citra validated by the volume at which the T. K. Aye ayo combo previously showed an overall response rate of about 12% presented at G. Rascal last year. And single agent data has been a little bit all over the map with accent nib ranging from an overall response rate of 14 to over 45%. In prior phase two trials and preservative. Previously showing an overall response rate of 14%. Neo ax was designed as a neo adjuvant trial investigating this I. O. T. K. I. Combination patients who were enrolled received both accented and the value map prior to surgery and If patients tolerated well at four weeks they were increased to seven mg accented V. I. D. From a starting dose of five and after a week eight they were permitted to increase to 10 mg exited the I. D. The primary endpoint was overall response rate greater than or equal to 25%. So here are the headline results from this trial accepted and available map did decrease the size of the primary tumor in the vast majority of patients by absolute terms. Other. This translated only to an overall The pr rate of 30%. So as you can see here from the waterfall plot many patients did have a slight decrease in size and of the patients who had no decrease in size. The majority of these people did not have increase either Among all patients. There was a median of 20% decrease in the dimension and the spider plot has shown. So I want to take just one or two minutes to point out that a lot of the work that was presented in the kidney cancer space at do you ask? Oh did come from our length center and I'm not gonna have time to go over each of these abstracts in the interest of time. But I'm going to present three slides just showing the breath of research currently being done by some of our colleagues. Um I think putting together all the kidney cancer abstracts. Approximately 1/5 to 1/6 involved authors in the learning Center which was international conference was was really heartwarming and so I welcome any discussion questions and comments. I'm gonna try to turn on my video but my video I think is currently disabled. So please minutes if you have any questions. Yeah so um Vincent I'll try to get you access. You can put your video on. But in the meantime, um, you know, we I I don't see any questions in the chat. So maybe um, all suppose one um Tony to you and and uh, you know, we'd love to hear your thoughts in general about any other abstracts from uh, could you pertaining to kidney cancer that you found interesting. But um, what with with, you know, 564. What are your thoughts? Um, in terms of how you uh, whether whether the updated data, um, that we saw at Ascot, do you change how you're thinking about it? If if at all, you know, or or you thinking that um, the sort of, you know, trend um, in overall survival um, is gonna bear out as we get more mature data. Any other findings from the updated data lock that are sort of changing how you think about giving a judgment pem brody or kidney cancer patients open and you're on mute. Not. You know, I think this is important when you talk achievement in general and solid tumors, you do have a population of patients that is over treated, no doubt whether it's breast, it's long, it's kidney, its bladder and it's important to know, you know, as long as the data progress, there has been some hesitancy, you know, adjuvant renal unlike a driven colorectal cancer for example, hasn't been really a reality until now with pembroke so any bit of more data is important. And remember this is six more months where patients are not on pembroke Lucimar, there is no active treatment. So what happens? So the results were very pleased with the result with both DFS and Os even with very little power for overall survival. So I in I think based on the approval, you have to certainly discuss it with patient now. Uh and hopefully we're gonna you know proceed to the next study to push again the envelope further in this in this disease. Yeah and I agree and you know there are several adjuvant trials and peri operative trials that are going to read out soon including checkmate 914 and so we're gonna hopefully see soon additional um carry operative immunotherapy data in this space. Um I'm actually a question for Tony um is there any patient in the world that you would now continue to offer a driven Senate nib for example the patient who has an absolute contraindications? Io it is so negative. Still alive in this setting. I mean I I have not patient that came with me on Senate and already I have continued you know for a second opinion but I have not, I mean the data with is very controversial despite you have one trial positive. You have many trials with the shift key that have been negative. Um and uh when we looked at the e cox studied a large study uh and we adjusted, you know, with the same eligibility criteria. We matched them in a way. There was no benefit coupled with quality of life and the absence of overall survival benefit. It was longer follow up. The answer is, is no, now that you have federalism ab as as an option and you know, whenever you have an autoimmune disease, you have to discuss how is it, is it active etcetera. If they're very active, they may not be eligible for any terror. Great thanks. And and and in the interest of time, I'm going to move us on in just a second but we have just another minute for for kidney cancer and Tony maybe I was maybe you could quickly comment for the group on on ongoing trials that you think or have the potential to, you know, change the landscape of kidney cancer, systemic therapy. So ongoing adjuvant trial where there is a trial with a jury, I mean I was gonna say a human or otherwise. Yeah, A given, there is a given that is Eliza mob, neo adjuvant tivo. And then a given Nevo. And there's an important study with a given six months of new volume of so that's duration. Because pem bro what Vincent presented the pembroke is one year, six months of Nepal, a mob or six months of naval hippie. So that is different. This is differentiated. Uh, you know, so those are the main one happening and we're working on intensifying therapy. Um, more than pembroke here regarding metastatic disease, I think. Um, winter is coming uh, and winter is the triplets. So we do have now trials with triplet. One of them finished accrual with Picabo versus Nouveau hippie Results expected at some point. And another one Very large pivotal trial was triplet with CTL A four inhibitor and have two inhibitors that are growing. Great. Thanks. Thank you. Vincent and Tony for for the presentation and discussing kidney cancer. Published March 16, 2022 Created by
