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ARANOTE and the Addition of Darolutamide to ADT in Metastatic Hormone-Sensitive Prostate Cancer - Fred Saad

June 9, 2026

Fred Saad presents updated ARANOTE analyses examining whether age or comorbidity burden modified the benefit of darolutamide added to ADT in metastatic hormone-sensitive prostate cancer. The original trial showed a 46% reduction in risk of rPFS or death. The new ASCO analyses found no difference in PSA response or time to PSA progression based on age or number of comorbidities, including patients with five or more concurrent conditions or medications. Drs. Saad and Sartor both note darolutamide's minimal drug-drug interaction profile as particularly relevant for older patients on multiple concomitant medications, and the adverse event profile in ARANOTE was essentially identical to ADT alone.

Biographies:

Fred Saad, CQ, MD, FRCS, FCAHS, Professor, Department of Surgery, Raymond Garneau Chair in Prostate Cancer, Director of Prostate Cancer Research, Director of GU Oncology, Université de Montréal, University of Montreal Hospital Centers, CRCHUM, Montréal, QC

A. Oliver Sartor, MD, Director, Transformational Prostate Cancer Research Center, East Jefferson General Hospital Cancer Center, Tulane University Cancer Center, New Orleans, LA


Read the Full Video Transcript

Oliver Sartor: Hi, I'm Oliver Sartor with UroToday and really a pleasure to be here at ASCO 2026 in Chicago with Fred Saad, who's led many important studies. We're going to be talking about a very important study, ARANOTE, that he'll be presenting some data with here. Fred's the Chief of Surgery at Montreal, and always a pleasure to have you, Fred.

Fred Saad: It's always a pleasure to be discussing with you, Oliver.

Oliver Sartor: Well, thank you. ARANOTE, I know what ARANOTE is. You know what ARANOTE is, but explain ARANOTE A little bit, and then what you presented here that's new and different than what was presented before.

Fred Saad: Right, so ARANOTE addressed the missing link of darolutamide in advanced prostate cancer. We already knew we can do a much better job adding darolutamide in non-metastatic CRPC, and we had data in combination with docetaxel to improve outcome over docetaxel and ADT. So the missing link is darolutamide alone, which was an attractive ARPI to be using in our patients that are metastatic hormone-sensitive. So the ARANOTE study was really randomizing patients to ADT plus darolutamide versus the standard of care ADT, which was still at the time the standard of care in many countries, excluding the US obviously, that had access. And the study was strongly positive in favor of adding darolutamide with a 46% reduction in the risk of radiographic progression-free survival or death. And all the other endpoints were in favor of darolutamide addition, whether it's time to mCRPC, time to PSA progression, time to pain progression, which we recently published in Lancet Oncology, and preserving quality of life was also an important endpoint and that was positively found with the addition of darolutamide over ADT alone.

Oliver Sartor: One of the things when I looked at the trial and really stood out to me was the adverse event rate and the side effects were essentially the same as a ADT alone. I mean, there was no added side effects from putting the darolutamide. I thought it was remarkable. I don't know if you might comment on that side effect.

Fred Saad: Yeah. Well, that was one of the main reasons I really wanted to do this study is that we had an adverse event profile in combination with docetaxel. So it was really hard to figure out what is the adverse event profile of darolutamide alone when you combine the mouse to an elephant while the elephant fills up the room. So this was really reassuring that we, as you said, saw very little difference with the placebo. I don't want to make cross-trial comparisons, but with the placebo, we saw almost no difference and surprisingly even less complained of fatigue on the darolutamide arm, reflecting the probably better cancer control than in the placebo and less discontinued darolutamide.

Oliver Sartor: I was very impressed with the data and the side effect profile. I was also impressed, just to comment about darolutamide for a second, the relative lack of drug interactions, which I think is very favorable. There are other ARPIs that create a little bit of a conundrum when you're dealing with the elderly population, many of whom on a number of drugs, maybe anticoagulants, et cetera, and the darolutamide is really devoid of that drug interaction profile.

Fred Saad: Exactly, and that's what we had done previously to this analysis is look at the outcome efficacy outcome regardless of con meds. And we looked at patients with less than five and patients with five or greater con meds, five or greater comorbidities and we saw no difference. So in terms of efficacy, so that really shows that patients were able to take the drug and maintain efficacy, whether it's rPFS, whether it's time to PSA progression, and whether it's also quality of life and adverse events, really no difference. And that was very reassuring.

Oliver Sartor: Let's come back to the 2026 ASCO presentation that you've given, and the question is what are the major findings of the ASCO presentation this year?

Fred Saad: Yeah, so this is to add on to the background and the previous analyses. So building on does age make a difference in terms of PSA response and time to PSA progression, age made no difference, the outcomes were similar. Whether they had less than five or five or greater comorbidities made no difference, the outcomes were the same in terms of PSA response and time to PSA progression. And also, in terms of number of comorbidities made no difference. Even patients with five or greater comorbid conditions made no difference in terms of getting the benefit of very profound PSA declines, and significant delays in PSA progression. So it just adds to the growing evidence that we don't need to withhold treatment because of the fear of multiple medications, multiple comorbidities, which is I think one of the reasons, and I blame my own specialty, urologists are maybe worried about adding to the burden of disease for patients that are comorbid or have multiple medications.

Oliver Sartor: So very nice conclusion, sort of icing on the cake the ARANOTE trial. A nice little exclamation point at the end of the sentence. So congratulations for another impactful presentation, not only to ASCO, but of course AUA and beyond for all the things you do.

Fred Saad: Thank you very much, Oliver.