Patient Preference Study Evaluating Darolutamide and Enzalutamide in Men with mCRPC - Karim Fizazi

June 4, 2021

In this conversation with Alicia Morgans, MD, MPH, Karim Fizazi shares trial results from the phase II ODENZA trial presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. ODENZA is a French prospective, randomized, open-label, multicenter, cross-over phase II trial of preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (CRPC). Darolutamide and enzalutamide are both next-generation androgen receptor inhibitors with demonstrated activity in men with castration-resistant prostate cancer (CRPC). Both have shown significant survival improvement, with different toxicity profiles. The ODENZA trial was designed to see if drug differences impact patient preference. Dr. Fizazi details the trial design, the primary endpoint: patient preference between the two treatments, as assessed by a questionnaire at week 24, and results of the study.


Karim Fizazi, MD, Ph.D., is a medical oncologist at Gustave Roussy, and a full professor in Oncology at the University of Paris-Saclay in Villejuif, France.

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU medical oncologist and associate professor of medicine at Northwestern University in Chicago in the United States. I'm so excited to have here with me today a good friend and colleague Dr. Karim Fizazi, who's a GU medical oncologist and professor of oncology at Gustave Roussy in Paris, France. Thank you so much for being here with me today, Dr. Fizazi,

Karim Fizazi: Thank you very much for inviting me today, Alicia, thank you.

Alicia Morgans: Of course. So I wanted to talk with you about one of your presentations at ASCO 2021. And this one's a really interesting one, I think from the perspective of really engaging patients to find out how they would make choices and what their preferences are about particular treatments for metastatic CRPC. The ODENZA trial looked at patients receiving darolutamide and enzalutamide to help sort out their thoughts. Can you tell us a little bit about this study?

Karim Fizazi: Right, sure. So, this study, ODENZA, is being presented at ASCO this year, my colleague, Dr. Emeline Colomba. And this was a randomized trial preference, patient preference trial, for men with metastatic castration-resistant prostate cancer, who are naive from any next-generation hormonal agents, such as enzalutamide, abiraterone, et cetera. And indeed, I think we all agreed that the current standard of care for most of these men with early mCRPC who have only received ADT or maybe ADT plus docetaxel for hormone sensitive disease is to receive a next-generation hormonal agents. The question is which one should we use in this setting and maybe in other settings. So this is why we did the trial. And actually the design is quite straightforward. All these patients were randomized to receive either enzalutamide, first for 12 weeks and then in absence of cancer progression, they were switched to received darolutamide for again 12 weeks or V over were randomized to V have a sequence darolutamide first and then enzalutamide.

At the end of 24 weeks, so when they had received both agents, of course we assessed cancer response, but also we asked patients if they had a preference between the two AR antagonists and if yes, why would they choose for one particular drug? And of course, except if there was a progression at this time, they could carry on with the drugs they had chosen. So, this is really the concept of this trial and we actually accrued 250 men in the trial so, quite a large trial, reasonable randomized trial, that was a multicenter trial that we conducted here in France. So that, I guess we have different population being represented in the trial. And what we found was that approximately 49% of patients chose darolutamide, as compared to 40% of men who preferred enzalumatide and 11% of them who actually didn't really had a preference between the two AR drugs.

The main reason why patients chose darolutamide was less tired so, a lower degree of fatigue being reported. And that was really by far the reason why they made their decision followed by some other aspects, such as quality of life, concentrations, mental concentrations, or these things. But, really fatigue was the main driver for the preference. Having said that the difference between the two groups, the two preference group was not significant so, this is only a trend. So, we cannot really say that more patients chose darolutamide over enzalutamide. Also, I think there was a trend favoring darolutamide I guess, where thinking things would go this way.

Alicia Morgans: That's really interesting and I know that you had a lot of patient reported outcomes integrated into this to really assess what might be driving the treatment decisions here. What were the domains that you looked into for patients to make this decision besides fatigue? What else were you assessing?

Karim Fizazi: So, we asked about 10 different questions, including less tired, easier to concentrate, feel down less often, could do more things, better quality of life, drug easier to take, some other things like this. And then there were also some open questions to the patients regarding some aspects we may have not think about, of course. And there were, of course, when you look at the details, you see a bunch of different things and actually sometimes you obviously see that it's more cancer related than drug related, of course, because at this time some patients could have already some signs of progressions, or on the other hand, they might favor also more of a drug that received first because they had some symptoms and they could tell that the drug was helping them to release them from their symptoms. So, of course you really have a number of different responses from patients, but again, the main driver for the preference toward darolutamide was less fatigue.

Alicia Morgans: That is so interesting actually. You make a great point that sometimes the thing that we see first, actually in a lot of decision-making and some work even in sort of constructing arguments to convince people different ways, primacy and recency can be two things that can kind of push you in one direction or another. And the thing you see first sometimes is the thing you sort of attach to especially if, as you said, it can affect your symptoms. How did you and the team sort that out, were there statistical methods that you could use to do that?

Karim Fizazi: Right, you know the first one was simply the randomization and having basically 125 patients in both groups. So, group receiving first daro and group receiving first enza strongly protects you against that. And also we adjust the findings from the trials, according to the drug that was received first in the analysis to make it stronger so you're right this is very important. One of the things we've been trying to do is to objectively assess whether these drugs are associated with cognitive impairment in the trial. And to do this we had patients fill in some tablets and having to think and to concentrate and to answer questions, et cetera, to truly assess their memory and their concentration, again, an objective way. We don't have the data as I'm speaking but we have to have them after the summer so if there is a difference between the two drugs, we should be able to show it, which is I think very important as well. Now, the last thing we looked at with the efficacy, at least at 12 weeks, because after that you have a crossover, you can't say much regarding PFS and OS. But, regarding response, for example, what we saw was that approximately the same number of men had a PSA 50 response, approximately 80% in both arms, which really shows us that these two drugs are very active.

Alicia Morgans: I agree and I think that's really reassuring in clinical care as well. We expect that they are essentially very similarly active, but to have that demonstrated in this trial, 250 people is actually pretty many people to do this sort of assessment of PFS or at least of PSA response. That's really, I think, very reassuring for us in clinic. So, thank you so much for taking the time to explain this and for doing work that isn't always considered so, very exciting to have a patient preference study reported out at ASCO 2021 and I really look forward to hearing continued data releases from this study. I think it would even be fascinating for someone to do a qualitative paper, just describing some of the things people wrote in that we might be missing as we're thinking about ways that patients consider differences between drugs or therapies that they're receiving. So lots of great data to come and lots of great data reported. Thank you so much for your time and for your efforts for these patients.

Karim Fizazi: Thank you very much, Alicia. Have a great day.

Alicia Morgans: You too.