Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I'm a Professor of Medicine and Director of Genitourinary Oncology Program at the Huntsman Cancer Institute, University of Utah. Today, I'd like to welcome Dr. Fred Saad, Professor and Chairman of Department of Surgery and Director of Genitourinary Oncology Program at the University of Montreal. Fred, welcome.

Fred Saad: Thanks, Neeraj. Always a pleasure to talk to you.

Neeraj Agarwal: Same here. I would like to, first of all, congratulate you for leading the ARANOTE study, the phase III trial which showed for the first time that darolutamide is effective without chemotherapy in the metastatic hormone-sensitive prostate cancer. So before we talk about your data being presented at the ASCO 2025 meeting, which Dr. Alicia Morgans is presenting as an oral presentation-- so congrats to both of you. But I'd like to first ask you about your take on the phase III ARANOTE trial, the results of that. How does it impact your practice? And then we can go to the quality of life data.

Fred Saad: Yeah, well, thanks for the opportunity, Neeraj. So exactly as you said. I mean, the reason we did ARANOTE was we had great data that darolutamide, in combination with docetaxel, improved survival over docetaxel and ADT alone. So the control arm for the ARASENS study was docetaxel and ADT. And the treatment arm was docetaxel ADT plus darolutamide. So all of the overall survival was being driven by darolutamide, 100%. But the question remained, darolutamide without docetaxel had to be done in that study.

And so we did a study, almost 700 patients, 2 to 1 randomization with an RPFS endpoint, since we already had two phase III studies with darolutamide that showed overall survival advantage. So we didn't feel we needed to do a study that was longer and took many more patients than 700 patients to prove the overall survival endpoint, since we already had two phase III studies. So the study was strongly positive, published recently, a 46% reduction in the risk of radiographic progression or death. And all the other secondary endpoints pointed in the right direction, delaying mCRPC, PSA progression, and even delaying pain progression, which is one of the focuses of what we're presenting here at ASCO.

Neeraj Agarwal: Thank you for talking about those data. Now let's move to the quality of life data, which you and Alicia Morgans and the team are presenting during the ASCO 2025 meeting. So could you please tell us about what quality of life tools were used, how you used them? How did you determine quality of life, as reported by the patients? And what were the results?

Fred Saad: Right. So quality of life, in many of the studies, was hard to show really any changes or differences of significance. But we were interested because patients came in with quite high PSA in ARANOTE, 21 median PSA, so pretty much the highest of all the mHSPC studies. And we had an opportunity to look at maintaining quality of life or delaying deterioration in quality of life and pain. And so looking at delays in pain progression, this was a significant reduction in pain progression in patients getting ARANOTE-- or getting darolutamide, 28% reduction in pain progression, which is something that we really want to maintain. Avoiding pain in patients is critically important.

And then looking at FACT-P, overall, maintaining quality of life was improved in the patients that got darolutamide. And looking specifically at what areas of quality of life, social, family well-being were preserved. Overall functional quality of life was preserved. And also in terms of delaying pain in the study was preserved and lengthened in patients that got darolutamide.

Neeraj Agarwal: So very consistent with the overall survival results, PSA responses. We expected to see preservation of quality of life. And that's what you finally showed in these data today, or presented during the ASCO meeting.

Fred Saad: Right.

Neeraj Agarwal: Well, anything else you'd like to include?

Fred Saad: Well, what we did include in this is correlating PSA response with maintaining quality of life, something that you had looked at even with apalutamide. And so we were curious. And we looked at patients not getting to below 0.2 versus patients getting to below 0.2 and even those getting to below 0.02. And patients getting below 0.2 or below 0.02 had a significant improvement in maintaining pain progression, maintaining quality of life compared to patients that remained above 0.2 at any time. So again, PSA, we say, is not that important, but it is important.

Looking at PSA responses is critically important because it not only predicts outcome in terms of mCRPC and survival and progression, but also in terms of how long you're going to maintain quality of life, which I think is very important.

Neeraj Agarwal: Absolutely, extremely important from patients' prognostication, counseling in the clinic. I think this is very important for our patients to know how their PSA responses are going to not only correlate with survival but also quality of life.

Fred Saad: Yeah. And as a small bonus, urinary symptoms were also significantly delayed in patients with darolutamide. We have to remember, these patients can progress locally. And that was also preserved and maintained with darolutamide.

Neeraj Agarwal: Well, congratulations to you, Dr. Morgans, and the whole team for these exciting results. And thank you for taking the time to join us today.

Fred Saad: Thank you very much.