Highlights in Urologic Oncology from GU ASCO 2022
David VanderWeele, MD, PhD, summarizes the highlights in urologic oncology from the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.
Featured Speaker:
Learn more about David VanderWeele, MD, PhD
David VanderWeele, MD, PhD
Dr. VanderWeele specializes in the treatment of genitourinary (GU) cancer from a medical oncology perspective. His research efforts have focused especially on altering the course of potentially lethal GU cancers using targeted therapies.Learn more about David VanderWeele, MD, PhD
Transcription:
Highlights in Urologic Oncology from GU ASCO 2022
Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.
And today we're talking about highlights in urologic oncology from the 2022 ASCO GU Cancers Symposium that was held February 17th in San Francisco. Our guest was among the featured speakers at the conference. Joining me is Dr. David VanderWeele. He's an Assistant Professor of Medicine in the Division of Hematology and Oncology at Northwestern Medicine. Dr. VanderWeele, it's a pleasure to have you with us today. Can you tell us a little bit about the highlights from the 2022 GU ASCO's Cancer Symposium? What sessions stood out for you?
David VanderWeele, MD, PhD (Guest): Great. Thank you for having me and great to be here. So, the GU ASCO Symposium covers a number of different cancers. The main three are prostate, bladder and kidney cancer. And so I wanted to highlight a few trials for each of those diseases that I think are most interesting or most impactful.
I think first off, probably the most impactful study is a large phase three study called the ARASENS trial. And that was presented by Dr. Matthew Smith. And it's for patients with metastatic hormone sensitive, prostate cancer and patients received ADT and docetaxel. And then with, or without darolutamide. This was a large phase three study with well over a thousand patients. And it was a positive study with pretty impressive data. The primary endpoint was overall survival and the hazard ratio for overall survival was 0.675 and also impressive the hazard ratio for time to castration resistance was less than 0.4, with very nice separation between those curves.
We don't really have the medians for overall survival yet, or even for time to castration resistance because the therapy was pretty effective. And so really, this is, I think the most impactful study and the one that's ready to change current practice right now.
Host: Dr. VanderWeele you were among the featured speakers at the conference, you co-chaired the prostate cancer oral abstract session. Can you summarize the key takeaways and notable highlights from that?
Dr. VanderWeele: Yeah. And this was in my biased opinion, one of the more exciting sessions, because of the studies that were highlighted there. So the ARASENS trial was one of the studies that was presented there. And of course that was very interesting and intriguing and great data for us as physicians. Other studies that were presented there were The PROpel study and the MAGNITUDE study, and both of these are studies for first-line metastatic castration resistant, prostate cancer. Both of them have a backbone of abiraterone. And then they add on a PARP inhibitor on top of that. And so they're large phase three studies with the PARP inhibitor versus placebo. In addition to abiraterone. This actually generated a lot of discussion because the PROpel study was a positive study overall, whereas the MAGNITUDE was a negative study. So PROpel was positive with Olaparib as the PARP inhibitor was actually open to all comers.
It's expected that patients with homologous recombination repair mutations, would have benefit from a PARP inhibitor, but this study happened to be open to all comers and then they kind of retrospectively identified which patients harbored these kinds of mutations. And actually it was positive overall study with the primary end point of progression radiographic progression-free survival. In contrast, the MAGNITUDE study was abiraterone with, or without niraparib, a different PARP inhibitor, and instead of being open to all comers, they first screened patients to see if they had a mutation and then divided them up into basically two different phase three studies, the ones for patients without any mutation in homologous recombination repair genes, was essentially a negative study was stopped early for futility. The portion that continued with 400 patients for those that did have mutations in homologous recombination repair genes. That was a positive study. But because the other portion of it was negative, there's a lot of discussion about what was the difference between these two studies?
Do we really think that Olaparib is a better PARP inhibitor than Naraparib or a better therapy for our patients? And so it generated a lot of discussion both in the session itself, and then carrying on, afterwards and in various venues.
Host: Fascinating. Dr. VanderWeele, can you expand a little bit about the metastatic castration resistant prostate cancer phase two study. Tell us a little bit about the trial at Northwestern Medicine and any other prostate cancer trials that are available at Northwestern.
Dr. VanderWeele: So we also had a poster presentation on a study that was an investigator initiated study supported by our SPORE grant and our SPORE program here for prostate cancer. Unfortunately it was a negative study, but it was targeting molecules that are important in sort of communication between tumor cells and the environment. So targeting efferens and F receptors. So it involved a soluble FB4 molecule to kind of block this sort of communication. It was a phase two study with 14 patients and unfortunately, it was stopped early, without progressing onto adding additional patients due to futility. The primary endpoint was PSA responses.
And actually we didn't see any PSA responses there. We also, had a presentation of another investigator initiated study, but this one is a trial in progress. So, it's a trial that is still ongoing. Well it's combining, the AR targeting drug darolutamide, along with the AKT inhibitor, ipatasertib.
And there's two parts to this study. One is in patients with castration resistant prostate cancer and is really looking at safety. And then it's going to move on into a phase two component looking at patients with high risk localized or locally advanced disease, in the neoadjuvant setting. So patients with high risk disease planning on undergoing prostatectomy, but at high risk of recurrence afterwards. And so that was presented as a trial that's still in progress. And in fact, that study is still open at Northwestern.
Host: Thank you so much. Dr. VanderWeele, as we get ready to wrap up, is there anything else, any other important information or learnings from this year's GU ASCO annual meeting that you want your colleagues who may not have been able to attend to know about?
Dr. VanderWeele: I think the, the most, important and sort of the practice changing studies where especially in prostate cancer. There was also some very interesting studies involving antibody drug conjugates for bladder cancer. So both Enfortumab Vedotin as well as sacituzumab govitecan, which are some of the newer agents approved for bladder cancer.
So looking at those things in different settings or, in different combinations and that's really an area of active research. And so none of what was presented is practice changing, but it just kind of highlights the directions that people are looking at. And people are thinking about, new roles for these newer agents.
I would say that for kidney cancer, there wasn't quite as much that was of significant interest. One thing that was kind of reassuring was an update on the keynote 564 study of adjuvant pembrolizumab for clear cell renal cell cancer. And this was encouraging and kind of looked even better than the initial presentation.
And so, that was reassuring for us who are thinking about or already advising patients on adjuvant pembrolizumab for their high risk kidney cancer.
Host: Wow. Thank you so much, Dr. VanderWeele for sharing the highlights in urologic oncology from the 2022 GU ASCO's Cancer Symposium. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. For updates on the latest medical advancements, breakthroughs and research, please follow us on your social channels. I'm Melanie Cole.
Highlights in Urologic Oncology from GU ASCO 2022
Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.
And today we're talking about highlights in urologic oncology from the 2022 ASCO GU Cancers Symposium that was held February 17th in San Francisco. Our guest was among the featured speakers at the conference. Joining me is Dr. David VanderWeele. He's an Assistant Professor of Medicine in the Division of Hematology and Oncology at Northwestern Medicine. Dr. VanderWeele, it's a pleasure to have you with us today. Can you tell us a little bit about the highlights from the 2022 GU ASCO's Cancer Symposium? What sessions stood out for you?
David VanderWeele, MD, PhD (Guest): Great. Thank you for having me and great to be here. So, the GU ASCO Symposium covers a number of different cancers. The main three are prostate, bladder and kidney cancer. And so I wanted to highlight a few trials for each of those diseases that I think are most interesting or most impactful.
I think first off, probably the most impactful study is a large phase three study called the ARASENS trial. And that was presented by Dr. Matthew Smith. And it's for patients with metastatic hormone sensitive, prostate cancer and patients received ADT and docetaxel. And then with, or without darolutamide. This was a large phase three study with well over a thousand patients. And it was a positive study with pretty impressive data. The primary endpoint was overall survival and the hazard ratio for overall survival was 0.675 and also impressive the hazard ratio for time to castration resistance was less than 0.4, with very nice separation between those curves.
We don't really have the medians for overall survival yet, or even for time to castration resistance because the therapy was pretty effective. And so really, this is, I think the most impactful study and the one that's ready to change current practice right now.
Host: Dr. VanderWeele you were among the featured speakers at the conference, you co-chaired the prostate cancer oral abstract session. Can you summarize the key takeaways and notable highlights from that?
Dr. VanderWeele: Yeah. And this was in my biased opinion, one of the more exciting sessions, because of the studies that were highlighted there. So the ARASENS trial was one of the studies that was presented there. And of course that was very interesting and intriguing and great data for us as physicians. Other studies that were presented there were The PROpel study and the MAGNITUDE study, and both of these are studies for first-line metastatic castration resistant, prostate cancer. Both of them have a backbone of abiraterone. And then they add on a PARP inhibitor on top of that. And so they're large phase three studies with the PARP inhibitor versus placebo. In addition to abiraterone. This actually generated a lot of discussion because the PROpel study was a positive study overall, whereas the MAGNITUDE was a negative study. So PROpel was positive with Olaparib as the PARP inhibitor was actually open to all comers.
It's expected that patients with homologous recombination repair mutations, would have benefit from a PARP inhibitor, but this study happened to be open to all comers and then they kind of retrospectively identified which patients harbored these kinds of mutations. And actually it was positive overall study with the primary end point of progression radiographic progression-free survival. In contrast, the MAGNITUDE study was abiraterone with, or without niraparib, a different PARP inhibitor, and instead of being open to all comers, they first screened patients to see if they had a mutation and then divided them up into basically two different phase three studies, the ones for patients without any mutation in homologous recombination repair genes, was essentially a negative study was stopped early for futility. The portion that continued with 400 patients for those that did have mutations in homologous recombination repair genes. That was a positive study. But because the other portion of it was negative, there's a lot of discussion about what was the difference between these two studies?
Do we really think that Olaparib is a better PARP inhibitor than Naraparib or a better therapy for our patients? And so it generated a lot of discussion both in the session itself, and then carrying on, afterwards and in various venues.
Host: Fascinating. Dr. VanderWeele, can you expand a little bit about the metastatic castration resistant prostate cancer phase two study. Tell us a little bit about the trial at Northwestern Medicine and any other prostate cancer trials that are available at Northwestern.
Dr. VanderWeele: So we also had a poster presentation on a study that was an investigator initiated study supported by our SPORE grant and our SPORE program here for prostate cancer. Unfortunately it was a negative study, but it was targeting molecules that are important in sort of communication between tumor cells and the environment. So targeting efferens and F receptors. So it involved a soluble FB4 molecule to kind of block this sort of communication. It was a phase two study with 14 patients and unfortunately, it was stopped early, without progressing onto adding additional patients due to futility. The primary endpoint was PSA responses.
And actually we didn't see any PSA responses there. We also, had a presentation of another investigator initiated study, but this one is a trial in progress. So, it's a trial that is still ongoing. Well it's combining, the AR targeting drug darolutamide, along with the AKT inhibitor, ipatasertib.
And there's two parts to this study. One is in patients with castration resistant prostate cancer and is really looking at safety. And then it's going to move on into a phase two component looking at patients with high risk localized or locally advanced disease, in the neoadjuvant setting. So patients with high risk disease planning on undergoing prostatectomy, but at high risk of recurrence afterwards. And so that was presented as a trial that's still in progress. And in fact, that study is still open at Northwestern.
Host: Thank you so much. Dr. VanderWeele, as we get ready to wrap up, is there anything else, any other important information or learnings from this year's GU ASCO annual meeting that you want your colleagues who may not have been able to attend to know about?
Dr. VanderWeele: I think the, the most, important and sort of the practice changing studies where especially in prostate cancer. There was also some very interesting studies involving antibody drug conjugates for bladder cancer. So both Enfortumab Vedotin as well as sacituzumab govitecan, which are some of the newer agents approved for bladder cancer.
So looking at those things in different settings or, in different combinations and that's really an area of active research. And so none of what was presented is practice changing, but it just kind of highlights the directions that people are looking at. And people are thinking about, new roles for these newer agents.
I would say that for kidney cancer, there wasn't quite as much that was of significant interest. One thing that was kind of reassuring was an update on the keynote 564 study of adjuvant pembrolizumab for clear cell renal cell cancer. And this was encouraging and kind of looked even better than the initial presentation.
And so, that was reassuring for us who are thinking about or already advising patients on adjuvant pembrolizumab for their high risk kidney cancer.
Host: Wow. Thank you so much, Dr. VanderWeele for sharing the highlights in urologic oncology from the 2022 GU ASCO's Cancer Symposium. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. For updates on the latest medical advancements, breakthroughs and research, please follow us on your social channels. I'm Melanie Cole.