Future Research and Development of Abiraterone Combination Therapies

Opinion
Video

In this video, experts share their opinion on the potential for novel combination therapies involving micronized abiraterone, particularly in conjunction with PARP inhibitors like olaparib or niraparib, as evidenced in clinical trials such as PROpel and MAGNITUDE. Additionally, they highlight other potential novel combinations like abiraterone with prednisolone and enzalutamide (STAMPEDE trial), and the integration of abiraterone in treatments involving radiation and androgen deprivation therapy (ADT).

Transcript:

Christopher M. Pieczonka, MD: We've got a couple of minutes left. I just want to switch a little bit to something that's near and dear to my heart, which is really what's your take on where the best research would be for the micronized abiraterone formulation. So right now it's on label for mCRPC. You know, what would you like to see if you had a gazillion dollars and you were going to end up giving it to people like you and me to do research, where would it be at?

Jose De La Cerda, MD, MPH: Oh man, so I think one of the biggest challenges in the clinical trials for micronized abiraterone is that due to the dosing differences, it's not often viewed as non-micronized or traditional abiraterone, despite being bioequivalent. So this limits the amount of trials available and the possibility of using micronized abiraterone in early disease states. One thing I would like to see is, you know, therapy. We're already using triplet therapy in the mCSPC state with abiraterone. And if you look at the NCCN guidelines, we're using abiraterone, ADT, and EBRT for patients that have very high risk. So I think this is a great opportunity to move micronized abiraterone earlier on in the disease states because people do well with it. Right now there is a phase one B trial coming out. It's looking at the pharmacogenetics and the food effect comparison of a single dose micronized abiraterone, which is 500 milligrams fasted versus a single dose micronized abiraterone at 125 milligrams in fed-state patients. And this is a new diagnosis of advanced prostate cancer. So there is stuff coming down the pipeline. I just think the real limitation has been that people don't look at it the same as non-micronized abiraterone, even though it feels like it's the same.

Christopher M. Pieczonka, MD: So I have an interesting question for you, which might be a little bit off the wall, but there's a variety of studies out there that now use abiraterone combination with other drugs. So we have the PROPEL study and we have MAGNITUDE. And so what would your take be if you had an appropriate patient? Would you consider the micronized abiraterone version in conjunction with the sort of the other drug?

Jose De La Cerda, MD, MPH: I don't see a difference now in the mCRPC state, so I don't feel like there would be anything that limits my use with a particular PARP inhibitor now. If you look at Niraparib and abiraterone, I mean, that's a single dual-action tablet, but you probably could use it with something like olaparib.

Christopher M. Pieczonka, MD: Then what about some of the STAMPEDE data? You touched on it earlier. I think in our practice in those very high-risk patients, we're counseling them about abiraterone. I suspect that you would say the same thing. So as for abiraterone, and if you can reach for the micronized version, would you be fearful of doing something that is within guidelines but is not unlabeled?

Jose De La Cerda, MD, MPH: Right, exactly. I mean, it's within guidelines, we've seen that there is a benefit and we've seen patients that have used the traditional abiraterone and do well with it. So I wouldn't be worried about so much starting it on a patient. I'd be a little hesitant about how the coverage would be and if they would even get it covered at that point. And I think that would be the number one thing that limits because, you know, the number one thing when it comes to this medication is just the limitation in terms of cost. And even if it does get covered, it doesn't mean a patient can afford it. And that's when we kind of discuss all the alternative options we have to help with that coverage. But for me, that's sort of the rate-limiting enzyme at the end of the day. It's just cost for the patient and the financial toxicity of it all.

Christopher M. Pieczonka, MD: And then one other question I think we'll wrap it up. Talk to me about not so much intensification. I think that in the last couple of years we've done a good job saying that ADT by itself is not enough, but what do you do? Have you been tempted to stop therapy if somebody's been undetectable PSA with abiraterone and ADT for years and you're wondering if they still need it or not? So I'm just curious to see what you think on something like that.

Jose De La Cerda, MD, MPH: I've done it before. I've done it just to kind of preserve the quality of life, give them the holiday and then see how they do. And it's actually seems to be pretty enduring. You know, you stop it and I've seen patients have no PSA clinically ready for progression after over a year and maybe start getting a little bump in their PSA rise. So then I restart them again. That's when it gets hard for the patient, because they start feeling a little bit better. They start feeling like themselves again, and then you have to sort of stop that. So the issue I have with that is not so much the recurrence, because I think we can control that. I think it's how the patient's reluctance to restart when they've been on something after they start feeling good. But I have done the holidays, especially if the, you know, their ECOGs start going up a little bit.

Christopher M. Pieczonka, MD: And then, I know we're probably over on time, but I have one other question too. So I'm thinking about the abiraterone with the radiation thing, just how you counsel your patients on that. So I can tell you, one of the things that I have found is that we have patients who are in androgen deprivation therapy kind of in the practice and they get referred into me and the patients may have an undetectable PSA, let's say, and then you say, oh, by the way, you should have been on abiraterone all along. So how do you deal with something like that, right? So if the data suggests, let's say, for those very high-risk prostate cancer patients, give ADT, give abiraterone, they're sitting in front of you and they say, "Doc, I'm having hot flashes, I don't want anything else." Like, how do you deal with that?

Jose De La Cerda, MD, MPH: You know, I think at that point, if there's no really sign of any clinical progression and the PSA is stable, I wouldn't just intensify just because. I'd wait to see how they respond, how they react, try to sort of minimize the impact on quality of life, do what I can to help with their ADT side effects, making sure that they're doing exercise, making sure they're getting vitamin D, going outside, giving megace if I have to, things of that nature. But if they've already responded with ADT, we've been doing it in the past for so many years and a lot of these patients don't progress. So I just kind of keep watching for now.

Christopher M. Pieczonka, MD: So I think we're pretty close to being up on time here. Kind of final thoughts for the community doctors, community urologists watching this series.

Jose De La Cerda, MD, MPH: I mean, abiraterone's been around for a long time now. I think we find that patients do fairly well with it. We're stopping testosterone production from the adrenal gland and from the testis tissue. We know that when we do that, we sort of decrease the risk of PSA progression and clinical progression, and it works great. I think what really matters is what a patient can afford because prostate cancer is an expensive disease. You're not just dealing with the NHTs, you're dealing with their bone health, you're dealing with their EBRT, you're dealing with chemotherapy, you're dealing with all these aspects of it, and that really just messes with the patient's quality of life and it really stresses the patients and their families out. So whenever you find a therapy that works, like abiraterone that we've known for many years, it's just a matter of making sure that we can make it as easy as we can for the patient.

Christopher M. Pieczonka, MD: Yeah, and I would piggyback that. And so my parting thought, I completely agree with everything and I really appreciate you kind of riffing back and forth with me this afternoon, is I want it to be easy on myself. So in my mind, something that's easy, that there's less potential of things that can go wrong and vis-a-vis you know fed and fasted state, worrying about dosing is something that you know, I would want to reach for and if I was the patient I wouldn't want to worry about kind of the timing in the interval about when to take it, you know, after meals, etc. So again, thank you for your time and for allowing us to spend some time together and have a good afternoon everybody. Absolutely. Thank you so much for having us.

*Video transcript AI-generated and reviewed by Urology Times® editorial staff.

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