Anticipated Data from Transformative Trials at ASCO GU 2022 - Oliver Sartor
January 6, 2022
A. Oliver Sartor, MD, Professor of Medicine and Medical Director, Tulane Cancer Center; C. E. and Bernadine Laborde Professor of Cancer Research, New Orleans, Louisiana
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
LYNPARZA® (olaparib) in Combination With Abiraterone Significantly Delayed Disease Progression in Patients Regardless of Biomarker Status in PROpel Phase 3 Trial in First-Line Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Phase III Investigational Trial of NUBEQA® (darolutamide) in Combination with Docetaxel and Androgen Deprivation Therapy (ADT) Meets Primary Endpoint of Significantly Increasing Overall Survival (OS) in Patients with mHSPC
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Alicia Morgans: Hi. My name is Alicia Morgans and I'm a GU Medical Oncologist at Dana-Farber Cancer Institute in Boston, in the US. I'm so excited to talk today with Dr. Sartor about GU ASCO 2022, which is happening in San Francisco from February 17th to 19th.
Oliver Sartor: Hi. And I'm Oliver Sartor, I'm Medical Director of the Tulane Cancer Center, medical oncologist. Delighted to be able to be here with you, Alicia, and look forward to GU ASCO and it is not that far away. We have some interesting results that I think we'll be able to be privy to, for those who are able to keep up with the meeting.
Alicia Morgans: Absolutely. And of course, UroToday is following the meeting and so will be able to give us very, very up to the minute coverage on everything that happens. Let's think through some of these abstracts. We did learn today that there are some really phenomenal abstracts that are going to be presented as oral presentations and of course, we'll have our array of posters and other rapid abstract discussions to think about. Some of the most exciting, I think in the prostate sphere include the PROpel trial. And we did see that this phase three trial had a press release already released a few months ago. Dr. Sartor, what is the PROpel trial?
Oliver Sartor: A really important trial. And I think everybody is incredibly familiar with the use of abiraterone in the first line metastatic CRPC space. This is kind of like COUGAR-302, part of the standard of practice. And in this case, they're unselected patients for DNA repair defects and the randomization is between abiraterone or abiraterone plus olaparib. I should say abiraterone prednisone, abiraterone prednisone plus olaparib. And interestingly, the press release indicates that it is a positive trial for RPFS, which was the endpoint. And we don't really know a lot of details but I'm looking forward to the opportunity to see more details. This could be a practice changing trial. I'm going to be looking for the magnitude of the RPFS and I'm also going to be looking at the adverse events and also going to be looking at overall survival and we're going to find that out to some degree at ASCO GU.
Alicia Morgans: I think that will be very exciting. And as you said, that press release suggested that there was an RPFS benefit actually across the population, which as you said, included all comers. The breakdown by mutational status, I think will also be so interesting and exciting. Along those lines, there's also going to be the presentation of another phase three, the MAGNITUDE study. Can you tell us a little bit about that?
Oliver Sartor: Sure. In some ways it's pretty similar. In this case, the PARP inhibitor is niraparib instead of olaparib but you're still going to be using the abiraterone prednisone. And again, it's metastatic CRPC. In this case however, there are two distinct cohorts that are going to be looked at. One of these are going to have the DNA repair defects and the other are not going to have the DNA repair defects. It's a very explicit split as opposed to the unselected patients that are present in PROpel. And again, we're going to be looking at RPFS as an endpoint. And again, I'm really looking forward to the results because this is where the rubber is going to meet the road. What about those patients who don't have a DNA repair defect, do they benefit? There's going to be about 600 patients in that subset and that'll be a really good look at the data. I know you're familiar with the fact that there is preliminary data in unselected patients for the combination of a PARP inhibitor and abiraterone and this really tests the question. I'm really looking forward to seeing what results might be.
Alicia Morgans:I completely agree. And to your point earlier, it's going to be really important for us as a field to look at the adverse events and the tolerability, because we know that abiraterone is well tolerated, does adding a PARP inhibitor make sense when we're really looking at the balance of benefit in terms of disease control, as well as how it's going to treat our patients in their day to day lives and that adverse event profile and the patient reported outcome. Really interesting stuff coming out. There's another press release that is preceding GU ASCO and this one's on the ARASENS trial, a phase three that we've been looking forward to. Can you tell us about this one, Dr. Sartor?
Oliver Sartor: Yeah, another very important trial. I think ever since the days of ADT docetaxel, both from STAMPEDE as well as in the ECOG studies, that we know that ADT docetaxel provides benefit over ADT alone, particularly in the high volume subsets. Here, you're going to be taking ADT docetaxel and adding in darolutamide, plus or minus darolutamide, in an effort to determine whether or not overall survival is improved. And guess what? The press release indicates that overall survival is improved with the addition of darolutamide to ADT docetaxel. Overall survival always gets my attention.
This is probably going to be very similar to the PEACE-1 trial, which used ADT docetaxel and then had plus or minus abiraterone also with overall survival as an endpoint. This is going to be a potential practice changing trial. I'm going to look at it carefully. Going to look at tolerability. And then one of the questions is going to be the other inverse sort of control group, what about if you had ADT darolutamide and then added in docetaxel? We don't have that as a control group. We did not have that as a control group in PEACE-1 with the ADT abiraterone plus or minus docetaxel. There's still going to be questions about the control group. This is a very important trial with an overall survival endpoint.
Alicia Morgans: Absolutely. And one that we've and kind of holding our breath for, for a few years, as we saw initial results from ENZAMET a few years ago and then saw really very positive results from the PEACE-1 trial, this is sort of in my mind, the tiebreaker of that kind of approach. And of course, we're still waiting on ENZAMET updated data by volume that maybe we'll see in the future too, that can help us with this particular disease state.
Oliver Sartor: Yeah. Let me comment about that a little bit because when the ENZAMET trial was initially analyzed, it really was relatively immature. And when we look at the PEACE-1, it's particularly that high volume subset that really seemed to benefit. We're going to be looking at that high versus low volume subset here in the ARASENS trial as well. But what I'll say is, look, when you have an overall survival endpoint, you stand up and you pay attention, at least I do.
Alicia Morgans: Absolutely. I think we all do. We're with you on that one for sure, Dr. Sartor. Now there is another trial, this one is called the PRESIDE trial, which is looking at patients who are treated with enzalutamide and then have progression. Can you tell us about this phase three trial being presented by Dr. Axel Merseburger?
Oliver Sartor: Sure. Again, sort of like COUGAR-302, we also have lots of experience with enzalutamide in the first line metastatic CRPC space. And this goes back to PREVAIL and the beautiful data that emerged from that study. In this case, everybody starts on enzalutamide for first line metastatic CRPC and then at the time of progression there's a randomization. Everybody gets docetaxel but half of the patients are going to continue on the enzalutamide and half of the patients get placebo and it's an RPFS endpoint. And again, we're going to be hearing about this trial for the first time at GU ASCO and I'll be paying attention into this one as well. Continuation of the enzalutamide in combination with docetaxel, maybe it's going to be important. I don't know.
Alicia Morgans: Well, I agree with you, Oliver. There is so much to look forward to and this is really just scratching the surface. Of course, there are some outstanding rapid abstracts, as well as poster presentations that we're going to see. And this is accompanied by lots of information that's going to be educational for us around the field, thinking about imaging advances, targeted therapies, new molecular targets among other things. Really exciting prostate cancer program. But let us not forget of course, that we're also going to see advances in urothelial carcinoma. I think that I am looking forward to the TROPHY- U-01 study that will be presented by Dr. Petros Grivas. And of course, in kidney cancer, we are going to see KEYNOTE-564 be presented this time with longer term follow up by Dr. Toni Choueiri. So much to really look forward to. Whether you can be there or not, the coverage will be here on UroToday. Any final comments, thoughts that you have Dr. Sartor?
Oliver Sartor: No, it's interesting, I hope I'm able to get out there in person. I know that it'll be a hybrid meeting with virtual possibilities as well but I'm looking forward to being able to get together with people again and seeing all my colleagues. I hope I'm able to go.
Alicia Morgans: I agree 100%. Let's stay safe all of us so that we can get there in person and really kind of get our lives back on track, get that GU ASCO 2022 on its way to being the best meeting ever. And we'll see you there if we can. And if we can't, we'll see you here on UroToday.