The ASCO Genitourinary (ASCO GU) and the Annual ASCO meetings are the leading educational and scientific events for oncologists, urologists, and the cancer team, providing the latest clinical and scientific data from clinical trials and basic and translational research in GU cancer. Thousands of abstracts summarizing state-of-the-art treatment modalities and novel therapies for patients with Prostate Cancer will be presented and it will be critical that educational programing provide learners with not only key data, but interpretation by faculty as to how best to incorporate into clinical practice.
Treatment Updates in Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)
Treatment Updates in Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)
Welcome to CME on ReachMD. This episode is part of our MinuteCE curriculum.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
Hello. So I'm Fred Saad, Professor and Chairman of Urology at the University of Montreal Hospital Center and Director of GU Oncology, and I'm very happy to be with my friend and colleague, Dan George. So Dan, can you do a brief introduction?
Yes, sure, Fred, thanks for having me. I'm Dan George. I'm a GU Medical Oncologist, Professor of Surgery and Urology and Medical Oncology at Duke University, and Director of GU Oncology here, and happy to join you, Fred.
Great. So, you know, I think the theme here is that ASCO was a huge meeting, over 40,000 participants this year, nice to see it back into full force. And there's been a lot of great stuff presented at ASCO. But there's some things that, you know, with all that was presented that might be under the radar, but some really interesting stuff coming out, where we're trying to learn from the real-world experience, it's one thing phase 3 studies, but in the real world, what's going on? And what can we expect?
And so, there's the DEAR study that I think you were a part of, and very involved in trying to get some idea in the real world how these drugs, apalutamide darolutamide, enzalutamide are working when used in the real world. So maybe you can share some of your insights in that study.
Yeah, Fred, you know, I mean, I think this is where real-world data can be really helpful in kind of filling the gaps. You know, we have 3 large phase 3 studies demonstrating the clinical benefits in metastasis-free survival and overall survival in nonmetastatic castrate-resistant prostate cancer. The ARAMIS trial, the SPARTAN trial, and the PROSPER study, all of them, you know, showed robust time – you know, improvements in time to metastasis-free survival and in early signals and overall survival benefit as well. So, it's clear we need to treat patients. But what's not so clear is, is there any difference between these agents? And, you know, when we just look, you know, within each study at its own, you know, interventional agent versus placebo, there are some differences. We do see, you know, proportionately less toxicity in the ARAMIS study, versus, you know, darolutamide versus it's placebo, versus, say, the SPARTAN trial, and apalutamide versus it's placebo and enzalutamide versus it's placebo in the PROSPER study. So there's reason to suspect that there could be differences in the tolerability of these agents in real-world practice.
And so the DEAR study was really to look just at that, at darolutamide, enzalutamide, apalutamide, in real-world evidence; hence the name. And it was a retrospective look at a really a national database of urology practices around the country where we looked at, you know, around 600 or so patients with - who were treated in the nonmetastatic castrate-resistant prostate cancer setting with these agents. And they had 6 months of lead-in data, they had treatment on drug in this space up until either disease progression or discontinuation because of toxicity. And it was interesting, because, you know, darolutamide was the last to be approved in this setting, but it's actually increased in its use in utility in this space recently. So we have relatively equal numbers of enzalutamide, darolutamide, less so with apalutamide.
But the real signal here was a composite endpoint of both stopping therapy because of either treatment discontinuation for toxicity or disease progression. And when we look at that, there was a clear signal for a longer time to discontinuation with darolutamide than with either the other two agents. And when we break it down by the different composites of that endpoint, just looking at the time to treatment discontinuation, or the time to disease progression, it's significant. It’s about a hazard ratio, you know, of 0.7. So there's about a 30%, longer a treatment effect. And, in fact, the median is not reached in the darolutamide group versus the other two. So and the other two are around, you know, 22, 24 months, median time to progression shorter than what we see in our clinical trial population.
But these patients are different. They're older, you know, the average age was median age was 80. And I think that's really reflective of our real-world population of patients. And to being able to see that maybe in that population of patients, we do see a little bit better tolerance, and maybe a little bit better, you know, dosing. We don't have insights into dosing but, but one of the reasons we might see a difference in efficacy could be because of the dose intensity in those populations with daro versus the other agents. So interesting data, really the only comparative data we have, between these agents and in this nonmetastatic castrate-resistant disease setting.
Yeah, well, that's really interesting. I think, outside of clinical trials, we need to learn from the real world of what's going on and try to - and this is really, really important across the field, to learn what we're doing well, and what we can improve on.
So there was another study looking at darolutamide, more specifically the DAROL study, that addressed some - that was reported earlier, and now this is an update. So maybe you just bring us up to date on this trial that maybe people aren't very much aware of.
Yeah, you know, DAROL, in many ways is kind of a complement to DEAR, because the DEAR was a retrospective analysis. This was a prospective analysis of outcomes in kind of an observational registry type format of patients with nonmetastatic castrate-resistant prostate cancer starting on darolutamide. And so it’s exclusive darolutamide.
The patient characteristics though were similar to what we saw in DEAR. The median age was 80, the median PSA coming on was relatively low, somewhere around 3 or so. And the median PSA doubling time was about 5.5 months, or a little bit longer PSA doubling time than what we saw on our clinical trials. And yet, we still see that median, you know, time to progression around 24 months. So it suggests that, you know, in the real world, our expectations around our patients outcomes might be a little bit different than what we see in our clinical trial practice. But again, we saw really well tolerance, we saw, you know, less than 5% toxicity rates from most toxicities associated with darolutamide. So even in, again, this older population in this prospective study, we're able to really document you know, good overall tolerance. Again, maybe a little bit, you know, shorter, you know, time to disease progression, but sort of in line with what we expect to see in this older population of patients.
That's great. And like I say, whenever I go around to the centers as a visiting professor, is when you're doing things now, registries are a great source of information. You know, and whether we're looking at all oligometastatic treatment with radiation and all the rest, I think it's going to be very hard to do trials in a lot of settings. And these registry type prospective studies really includes patients that are often not in clinical trials.
So congratulations to both of these trials and thanks for sharing that insight, Dan.
You have been listening to CME on ReachMD. This activity is jointly provided by Global Learning Collaborative (GLC) and TotalCME, Inc. and is part of our MinuteCE curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/CME. Thank you for listening.
This activity has been designed to meet the educational needs of the interprofessional team, including Medical Oncologists, Urologists, Nurses, Pharmacists as well as other clinicians involved in the management of patients with prostate cancer.
After participating in this educational activity, participants should be better able to:
- Apply recent practice-changing data to inform sequencing decisions and treatment strategies for patients with prostate cancer
In support of improving patient care, this activity has been planned and implemented by Global Learning Collaborative (GLC) and TotalCME, Inc. GLC is jointly accredited by the American Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE) and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
This activity was planned by and for the healthcare team, and learners will receive 1.0 Interprofessional Continuing Education (IPCE) credit for learning and change.
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all educational programs.
The following faculty have disclosed:
Daniel J. George, MD, faculty for this educational event, is a contracted researcher for Astellas, AstraZeneca, Bayer H/C Pharmaceuticals, BMS, Calithera, Exelixis, Inc, Janssen, Novartis, Pfizer, and Sanofi; and receives consulting fees from Novartis, Astellas, AstraZeneca, AVEO Pharmaceuticals, Bayer Pharmaceuticals, Brown and James Atty, Eisa, Exelixis, Inc, IdeoOncology, Janssen, Medscape Education, Merck Sharp & Dohme, Michael J Hennessey Associates, Myovant Sciences, Inc, Nektar Therapeutics, Pfizer, Propella TX, Sanofi, Seattle Genetics, UroGPO, UroToday WebMD, WilmerHale and Xcures.
Fred Saad, MD, FRCS, faculty for this educational event, is a contracted researcher for Astellas, AstraZeneca, Bayer, Janssen, Myovant, Pfizer, Novartis/AAA, Point, BMS, and Sanofi; and receives consulting fees from Astellas, Astrazeneca, Bayer, Janssen, Myovant, Pfizer, Novartis/AAA, Point, BMS, Tolmar, and Abbvie.
The following planners/reviewers/managers have disclosed:
Megan Reimann, PharmD, BCOP, planner for this educational event, has no relevant financial relationships with ineligible companies.
William Mencia, MD, FACEHP, CHCP, reviewer for this educational event, has no relevant financial relationships with ineligible companies.
TotalCME, Inc. planners and managers have no relevant commercial relationships to disclose.
All the relevant financial relationships for these individuals have been mitigated.
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and TotalCME, Inc. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient's conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to link to a site outside of MedEd On The Go you are subject to the terms and conditions of use, including copyright and licensing restrictions, of that site.
Reproduction of this material is not permitted without written permission from the copyright owner.
This activity is supported by independent educational grants from Bayer and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.
Jointly provided by Global Learning Collaborative (GLC) and TotalCME, Inc.
This activity is FREE to all participants.
During the period 3/3/2023 through 3/3/2024, registered participants wishing to receive continuing education credit for this activity must follow these steps:
1. Read the learning objectives and faculty disclosures.
2. Answer a pre-program question.
3. View the program.
4. Complete the post-test with a score of 100%.
5. Complete activity evaluation.
6. Apply for credit and either bank your credits or print your certificate.
For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service. This may require you to add or update the e-profile ID/date of birth information saved in your account.