mCRPC in focus
Transcript: mCRPC update: Q&A
Dr Neeraj Agarwal, Professor Karim Fizazi, Dr Bárbara Vieira Lima Aguiar Melão, and Professor Axel Merseburger
All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
And now move on to the questions here from the audience. So thank you very much for putting in your questions here. One of the first question is, "How do you translate clinical findings into updated, in the clinical practise? I want to assure the latest work inform my patient's treatment." I think this is pretty broad question. So I will like to probably ask Karim, translation of these findings. So we are seeing these major phase 3 trials being presented, level one evidence, and is it really being translated into community across the world? So this is a pretty big topic. So like to hear your viewpoints.
Sure, now, this is why it's probably so important to get data in clinical trials about what's clearly related to patient's life, including quality of life, pain, scattered related events in prostate cancer because it's really metastatic prostate cancer is a [indistinct] disease in most cases. This is really telling us whether we are helping patients, yes or no. PFS, you know, is something, but again, you may, as Axel rightly said it, you may argue whether a significant PFS benefit actually translate into true benefit in older patients, especially when you use the same treatment in other routine practise in weaker patients and with more comorbidities. So this is why I think we should put all the thoughts in clinical trials, capturing information regarding data which are not related to PFS or overall survival. Of course, we're all happy when overall survival is improved, but it's hard, I mean, the bar is very high. And if we want to have average treatment on the market, we just need to demonstrate that we're directly helping patients besides overall survival when the bar is just too high. So this would really be my answer. Now, generally speaking, I'm not a big fan of what we call real-world studies, which is just a collection of given treatment in all the patients.
I think there is one exception, and the exception is that these trials or these studies may actually be able to detect rare toxicities. So in other words, if you did your trial in, say, 500 men or women, and you showed that X is better than Y, and if a rare toxicity occurs in just one out of 1,000 patients, but it's a bad one, you wanna know it. And actually, those real-world studies will tell you if they are able to accrue, say, 1,000, 2,000, 3,000 patients. So that's really where they have values. But otherwise, usually they're not very important scientifically and clinically to me at least. I know that the agencies and the health system wants to see them and wants to see, I guess, reassuring data in their environment, so in their countries, with more patients. But you know, usually as Axel just said it, it typically, you know, shows the same data that we saw in the trials with just a weaker efficacy because the selection of patients is a weaker one. But usually, they're not super interesting. But I mean, I may be biassed obviously.
Yeah, and I'll like to, thank you, Karim, and I'll like to share another aspect about translation of these level one evidence into clinical practise at the community level. And studies have shown that despite level-one evidence out there, being out there for many years, many of our colleagues may not be utilising them in our patients. And the results are multifold. There's not one factor, it's not. It is possible that real-world patients are frailer, sicker, and they may not be eligible to receive these treatments. But we also know that many of our busy colleagues in the community don't have time to join us in these big conferences which are happening in different parts of the world or even regional conferences. And that brings up the idea of disseminating the information, the clinical data, through the digital media, like we are doing right now. So getting to the real-world practitioners, how can we get to them? How can we bring the data to those busy practitioners across the world rather than expecting them to come to these large meetings? So I think kudos to Medthority and many other educational forums, which are already doing it. So I think this is very important, what we are doing here right now. I will go to the next question. What is the best time to look for BRCA1 and BRCA2 mutation in a patient with metastatic prostate cancer? Do we test for them in mHSPC setting? Do we wait for mCRPC setting? So Axel, I'll come to you. What do you think? When should we test for these mutations?
Ideally, even earlier in all metastatic patients, but it depends really on the approval and the reimbursement status in each country. So I cannot just answer very broadly here because it's depending on, for example, for olaparib monotherapy in mCRPC, the testing for Europe and Germany is approved and reimbursed, but it can be very different throughout the countries. And then we have combinations, like enzalutamide and talazoparib, where you don't need to test, at least, in Europe. So you just start and then test. So I think to come back to your question, I think from the point of mHSPC towards mCRPC, that's the best point. We really want to know what the biomarker status with regards to HRR status is. That's my opinion. Happy to hear yours.
Barbara, when should we test?
Oh, as soon as possible. But as Axel said, there is a reimbursement issue that we have to analyse. And I'm looking forward for the results for the studies from PARP inhibitor bringing, that has been brought early on. So probably, I truly believe that target therapy, I truly believe BRCA-mutated patients are HRR, some of them, of these mutations have greater benefits. So I really think they have to receive PARP inhibitors early on, but then of course, we have to wait for these results, but as soon as possible. Once the patient progress to mCRPC, sometimes we need another biopsies. We are urologist, Axel. So perhaps radical prostatectomy is the only specimen. It's, I don't know, 10 years has passed, and we cannot use this material, and we need new biopsies, and sometimes the metastatic sites are just not good enough for new biopsies. So as soon as possible in advanced prostate cancer and looking forward for new results for PARP inhibitor in early settings.
And this may be a moot point once if we have hope, we have positive results on the ongoing metastatic hormone-sensitive prostate cancer trials, which are using PARP inhibitors, AKT inhibitors. And if those trials are positive, they are being tested in biomarker-positive patients. So we may be testing them upfront. I'll come to a very nice quality of life question, Karim. I'll bring to your attention. And this is what is the success rate in terms of improvement of quality of life in the current treatment of metastatic prostate cancer? And I'll make it a little bit broad based. We use different questionnaires, different methods to assess quality of life in different trials. So you mentioned quality of life as being very important. So what is your take on the value of assessing quality of life in prostate cancer clinical trials?
Sure, I think we have quite robust questionnaires for patients who are sick, symptomatic, bone pain, you know, all those things in advanced stages. And actually when we have a good treatment, we are actually able to show meaningful benefit in quality of life. You know, I mentioned VISION, for example. There was clear benefit in quality of life with lutetium PSMA in VISION, again, in very sick patients. Another obvious example that comes to my mind is LATITUDE when we selected high-risk metastatic castration-centric disease. Using abiraterone is associated with a clear improvement in quality of life or a clear improvement in terms of time to deterioration in quality of life versus ADT alone. So again, when you're selecting a subgroup of men with really bad disease, all the questionnaires are pretty good to show meaningful differences in quality of life. On the other hand, if you're selecting help in a quite healthy man, actually, it's...
And when, you know, quality of life becomes much more subtle, it's not really a big symptoms which is harming your daily quality of life, I think all the questionnaires are very imperfect, and we should actually try to improve that. Perhaps asking more upfront at the individual level what is important to that specific gentleman or woman, of course, for his or her quality of life, which is could be actually different to someone else. I'm sure that if you're asking us, Neeraj, Axel, Barbara, and I, what's important in our respective quality of life, we may provide you different answers. So that might be actually helpful to design new quality of life assessments for people who are, say, more healthy. But I think this is a very important field. If we want to better capture how to best help all the patients.
Very interesting that most of the questionnaires currently are really applicable to those patients who have a lot of symptoms, they are sick, but healthy patients. And hopefully, we'll see more and more healthier or robust patients going on clinical trial because when they have newly diagnosed prostate cancer, they really don't have as many symptoms. So we may have to develop quality of life questionnaires or a better way to assess their quality of life. Such an important point. I think we'll have time for one more question. We have quite a few questions in hormone-sensitive metastatic prostate cancer setting. And we do respect because we're focusing on mCRPC setting today, I'll like to exclude that, but we're always available to answer those questions offline. If you can contact us through, you know, through the organiser of this conference, we'll be happy to take them later. And the last question I'll bring up is, maybe, Axel, I can ask you a more like a concluding question, overarching question: how do you see the field of metastatic prostate cancer? Or rather, let me rephrase: how do you see the field of localised high-risk prostate cancer or metastatic prostate cancer or mCRPC? As far as therapeutics are concerned, how do you see this field evolving in the med field?
Thanks, Neeraj, a difficult question for the end, but I think we've come further since the last two decades from just ADT to, like, a very large armamentarium how we treat those patients, so that is great. And now, the perspective all went to treatment intensification, and I think we should work on treatment optimisation. So there are trials to de-intensify treatment in mHSPC. For example, leaving away the ADT, as you said. Men don't like chemotherapy, and men don't like to get castrated. And I think this in combination what Barbara, you and Karim mentioned for new developments, phase 1 trials, catches my excitement here in the next upcoming conferences. So I hope treatment optimisation and not intensification and just really use what we have with best quality of life. And sometimes it means that, like for example, Barbara and myself will probably have to work with you guys in oncology very closely together to do this preoperative treatment in high-risk prostate cancer, still get in with radiation therapy, and maybe even with our scalpel and our robot. So I think it's a very good multidisciplinary collaboration. And I'm looking forward to see what's happening in the field of prostate cancer. Still very exciting. Thank you for letting me join this wonderful discussion.
Thank you, Axel. Karim, any concluding remarks on the field of how we are moving in the field of metastatic prostate cancer?
I feel, well, I mostly support what was said. I think that for metastatic disease, we still need to demonstrate that we can cure some patients. And until we do so, I think treatment intensification or strategies to improve the efficacy will remain the key question. You know, for example, regarding the question of deescalation, I think we should be very cautious and really select very, very, very good candidate for deescalation when it comes to metastatic disease. You know, the last time we did collectively was at the time of a SWOP trial, which randomised intermittent versus continuous ADT. And even if the conclusion is that it's inconclusive, patients who received continuous treatment actually lived one year more than those who were in the intermittent arm. So we need to be careful. And I, again, patients with metastatic disease still die. So I think we need really to optimise, but optimise meaning improve the efficacy of all the treatments / reduce toxicity if we can, but not necessarily deescalate in most patients with metastatic disease.
Now, for patients without metastatic disease, clearly, with Axel, I think we should actually think about deescalating, at least in some patients that we can select. This is true, for example, duration of systemic treatments. Probably we will use more and more AR pathway inhibitor in earlier stages, but perhaps not forever. Not, you know, not continuously, or for three years, or for five years, or something like that. We can actually think about shorter treatments. It may also apply to local treatments. I think we're still using too many local treatments which are too toxic in too many patients who have really no need for disease. So we should think about optimising that, and hopefully, biomarker will help us.
I'm not quite sure. I think we might have lost Dr Agarwal, at least his camera. So maybe Barbara, your final comments.
Oh, I agree with all your comments. We need biomarkers. We need biomarkers to better select treatment. We need biomarkers to assess a treatment response. So we need good biomarkers. Thinking about the intensification, we need biomarkers to make sure patients are going well, and perhaps, these biomarkers following treatment response will allow us to do that, or intensify, or de-intensify, or even change treatment before the biochemical radiographic progressions. Perhaps in the future, we will be able to do it. So I'm enthusiastic of target therapies. I think it's a way to deliver a better treatment with elasticity, so we have to think about quality of life in these patients. We have to deliver more quality of life because of patient's, of course, survival benefits, it's important, but also, we have to met a patient's goals, not only ours.
Yeah, I was having some problem with my camera, so apologise. I think we can conclude our session. This has been a wonderful discussion. We actually were able to review a lot of abstracts from ASCO and GU-ASCO in 2024. And again, thank you, audience, for sharing your questions. And hope it was enriching experience for all of you. So thank you to the faculty again for sharing their wonderful insights. It is always a learning experience for me to hear all of you. And with that, I'll like to conclude the session. Thank you very much.
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