Episode 48: Renal and Prostate Cancer ASCO GU Updates

Dr. Shilpa Gupta of Cleveland Clinic joins Healthcare Unfiltered EXPRESS to share three major abstracts from the ASCO-GU-2026 meeting that could change clinical practice in kidney and prostate cancers. Dr. Gupta brings this data home by explaining their impact on real-world practices. Check these out, subscribe, review, and join the conversation.

Transcript

SPEAKER_01 0:01

Welcome to the Healthcare Unfiltered Express, where I conduct short video interviews back with relevant and timely information that you cannot miss. So sit back and enjoy the show. Well, finally we made it happen. Shilta, welcome to the show.

SPEAKER_00 0:24

Thank you, Charlie, for having me. It's my honor to be on your show.

SPEAKER_01 0:27

And congratulations. I have to say this. I congratulate you before I went on the air, but I have to do this on the air because I'm very happy. Congratulations on the award at the EAU. So uh briefly, what was the award? So I get a brag about my friends winning.

SPEAKER_00 0:42

No, thanks for um your kind support. You know, it was um I got the European Urology Ambassador Award for service to the EU family of journals and the EAU. And I was really uh very humbled and honored to receive that, and it was um very kind of them to choose me. So Dr. Briganti, who's the chief editor, um, and then Dr. Arnulf, uh, who's um the EAU um president. So it was really nice recognition. I'm grateful.

SPEAKER_01 1:13

Your work pays off and it's well deserved.

SPEAKER_00 1:16

Thank you.

SPEAKER_01 1:17

Um it's no easy task to try to uh tell us a bit of what happened at ASCO GU, but uh I thought we'll spend a few minutes talking about what caught your attention from ASCO GU, specifically focused on kidney cancer and prostate cancer. Um, things that you believe could have practical implications for practitioners, for fellows, for residents, even for again uh academic research. So um take us through kidney cancer stuff.

SPEAKER_00 1:46

Yeah, thanks, Shari. So um, you know, we had two exciting uh studies that were presented at ASCO GU, both of them being the light spark studies. So one was the randomized phase three light spark O22 study, which Dr. Tony Shwery uh presented. As you know, based on the keynote 564, adjuvant PembrolyMap is the standard of care which improves overall survival compared to uh um, you know, placebo. And um, so that's the current standard. And the purpose of this study was to see if adding the HIF-alpha inhibitor Belzudiphan to Pembro can improve upon that. So Pembroke was the control arm uh in this study. So this was a phase um phase three study, um, really big study, you know, over 1,840 patients. And these are all patients who had uh clear cell RCC, uh M0, and intermediate to high grade or high grade. And also these included patients who had resected M1 disease with no evidence of disease, and the window of that was actually two years as opposed to uh one year. So in this, they were randomized to Pembroke and Belzudevan um for um you know 54 weeks or uh up to 54 weeks versus PERO and placebo primary endpoint was disease-free survival, and um of the 1841 patients uh you know they were enrolled, the hazard ratio for disease-free survival was uh uh has 0.72, which is quite remarkable, with a p-value of 0.0003. And um, if if we look at the uh forest plot, you know, the disease-free survival benefit was seen across the board uh uh regardless of the risk uh category, but it was most pronounced in the intermediate to high risk patients. And the overall survival is not mature, but the hazard ratio was 0.78, and we'll have to see whether this translates into improvement of overall survival and follow-up uh data analyses. I would say um the toxicities were as expected. You know, there's more rates of anemia given there's the HIF alpha inhibitor, and there were some um hypoxia was uh more obviously 4.6% versus 0%. So I think this is uh a good attempt to add um a drug which is relatively not um, you know, uh not like a TKI, but there are these unique toxicities of anemia and hypoxia for which we use EPO and blood transfusion. And uh I think we'll see if this becomes uh a regimen in the future.

SPEAKER_01 4:39

Shilpa, I'm intrigued by the subset of patients who actually had a resected M1 that were NED. Um was this subset looked at separately to see if there's any difference specifically because that lag time of a couple of years before you put them on the trial seems a bit too long for my taste.

SPEAKER_00 5:03

Yeah, yeah. And you know, that's I think um um at the EAU we had the Meet the Euromigos uh live challenge, the Euromigos uh uh event, and I asked that question too. So that was not a whole lot of patience, honestly. I would say total were about uh um you know uh M1NED were um 36 in each arm, I believe. But yeah, but the thing is, you know, you also wonder that if somebody's M1, you know, should they not be getting a doublet, right, of IOIO or IOTKI, right? If they are at very high risk. Um but in this case, looks like uh because the window was so long, could be that their disease is so indolent. And sometimes, like to your to your point, do they really need anything at that point? And in the forest plot, actually, it did not show that it was it was not really favoring Pemro and the Zurif and uh it was right uh at the boundary. So I I also doubt and wonder if that's just a distraction from the larger data set.

SPEAKER_01 6:13

Okay, next one.

SPEAKER_00 6:15

So the other uh uh exciting abstract was uh Light Spark O11 study, which was presented by Dr. Bob Mozart. And this is a phase three study, also Belzudivan-based, so addressing Belzudivan plus Lenvatineb versus Cabozantineib for uh patients with uh metastatic RCC after a checkpoint inhibitor. And uh as you know, you know, we used VEGFTKIs um in this setting a lot, and they chose caboxantineb as the control. Um, and this study had um around uh just a little shy of 800 patients who received Belzulivan and Lenvatine versus Kabozantineb 60 milligrams a day, and dual primary endpoints were progression fee survival and overall survival. And um when Dr. Moza presented this data, um the median progression fee survival was 14.8 months with the combination versus 10.7 months with caboxantinep hazard ratio 0.7. So really curve separated out pretty early, and that was uh remarkable. And it pretty much benefited uh across the subgroups. I'll say more benefit seen in the favorable and intermediate as opposed to uh the poor risk. And at the time of the second interim analysis, the overall survival was um not significant, but the hazard ratio was 0.85, you know. So it's 34.9 months in the combination versus 27.6 in Kev's antinep. And the response rates, as you know, you know, um Zoodifan doesn't really add much to the responses, but the objective response rates were 52.6 versus 40%. But we do know that Lenvatinep does lead to higher response rates. So I don't know uh what was driving the responses mainly. And duration of response was pretty impressive, almost doubled, like 23 months versus 12 months. And um, so you know, when we look at the safety profile again, consistent with the profiles of individual uh uh drugs here, hypoxia as the key side effect in the combination arm, and um, you know, there's diarrhea in the cabozantineb arm. So I think um, you know, Belzudifan is thought of as a good partner because of the non-overlapping toxicities and very predictable side effects, which one can manage with uh EPO and blood transfusions, and I think um this adds to the efficacy of Len Vadinab.

SPEAKER_01 8:53

So this is this is first line, huh?

SPEAKER_00 8:56

This is after a checkpoint in a bit, I think.

SPEAKER_01 8:59

So in the second line. I see. So um do you think it represents uh just another option, or do you think it becomes almost standard of care?

SPEAKER_00 9:09

I think you know it's uh if if because they've chosen cabozantineb, right? If if somebody has um um is planning to use cabozantineb, I think the combination does show benefit, right? So it it would be a standard of care, I would think. And uh it's important to see that Belzutivan is pretty much moving early, right? Right now it's in very late settings when we've pretty much exhausted other um treatments. In this, although I'll say less than or equal to two systemic therapies were allowed. So they they couldn't have had prior Kabozantinep or Belzutifan or Lenvatineb. So if they even received a doublet first and then a second line, which is another TKI, they could still go on this study. So I think I think it's just um a strategy to move this sooner rather than give Lenvatineb, uh, let's say if somebody's using Lenvatineb in third line setting and then they use Belzutifan, this is just bringing them together, I guess. That's how I look at it.

SPEAKER_01 10:18

Um two exciting abstracts in kidney cancer. Anything struck you in prostate cancer? And then um, I think we'll probably wrap up.

SPEAKER_00 10:27

Yeah, so no, I like how you're going with this uh, you know, uh fast pace. So prostate cancer, uh, as you know, we saw the PSMA addition data at um the ESMO meeting, right? And at this um meeting, I'll say that the key study that took out was the final overall survival of the PS3 trial. Okay, this was uh a humongous effort um that was undertaken by the um study team. And so basically, what this study is in CRPC patients with metastatic disease, uh they looked at comparing enzyutamide and radium versus enzyutamide. And this patient population, as you know, needs to have bone metastases, no visceral metastases, they have to be asymptomatic or minimally symptomatic, and um they have to be on ADT and um no prior treatment with radium or enzyutamide. And I want to highlight here, you know, in the past we've seen that when you combine the radium with everydron, the outcomes were worse, right? The study was terminated and there were more side effects, more fractures. So this was important that combination of enzyutamide and radium does not suffer from those issues. And could be that, you know, with abirateron, we also use steroids, and enzyleutamide is steroid sparing. Primary endpoint was uh radiographic uh progression fee survival, and there were about uh 446 patients um who were enrolled, and in this they showed the final overall um survival um data, and it was superior with the combination. And um so if you look at the details of the combination, you know, 38 months versus 32 months hazard ratio 0.76. And um this is um, you know, impressive data because this study brings back uh radium to the forefront. You know, in the US, we are now using more and more of lutetium, and then we still use radium, but it has not been in much use, right, ever since lutetium came around. And this offers a good option, a very uh uh very viable treatment option. And uh there were no new safety signals. Uh side effects were a little more, you know, adding enzyutamide uh does add to that uh with the radium. Some like 28% patients had grade 3 or higher uh side effects versus 19%. And the most common side effects, I would say, in the combination, which struck out were fatigue, which was more in the combination, some increased fractures 5.5% versus 1%, anemia was higher, um, and uh decreased weight. So I think um, you know, but there's also a special interest side effect of myelodysplastic syndrome, one with AML, one with CML in the combination arm. And we have to be careful with these treatments, as you know, you know, even with pluvicto, we see uh myelodysplastic issues, marofibrosis in some settings. So I think um in this median follow-up of over a year, this data is important. That combination did lead to significant improvement in overall survival, and um the improvement in the RPFS was confirmed as well, and uh the overall um RPFS improved from 16 to 19 months. So I think it represents a great option, especially I think looking at it globally, um, that it was um, you know, places where they don't have lutetium, for example, this is still a very viable option.

SPEAKER_01 14:20

Amazing. Ken, thank you enough. This was really fast, quick, and to the point. And these three abstracts really have a lot of clinical implications. I really appreciate you coming on, Shelka.

SPEAKER_00 14:31

Thank you, Charlie. My honor. Hope to see you soon.

SPEAKER_01 14:35

Thank you for listening to this edition of Healthcare Unfiltered Express. Until next time, take care.