PARASEC Study Reveals Real-World Treatment Patterns After Darolutamide in ARAMIS Trial - Javier Puente
March 27, 2025
Zachary Klaassen hosts Javier Puente to discuss the PARASEC trial. Dr. Puente describes this retrospective observational study examining treatment patterns of patients who received darolutamide in the Spanish cohort of the ARAMIS trial after progression to metastatic castration-resistant prostate cancer (mCRPC). From the 85 evaluable patients, he highlights several key findings: 29% received no further treatment after progressing to mCRPC, possibly due to the elderly population (median age 76 at enrollment); contrary to guideline recommendations about switching mechanisms of action, 63% received abiraterone as first-line mCRPC therapy; chemotherapy was frequently delayed to second-line (76%); and only 20% received bone-protective agents. Dr. Puente notes these real-world patterns reveal significant guideline-discordant practices and suggests better standardized treatment algorithms and continuing medical education are needed to optimize patient care across specialties.
Biographies:
Javier Puente, MD, PhD, Medical Oncology Department, Hospital Clínico San Carlos
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Javier Puente, MD, PhD, Medical Oncology Department, Hospital Clínico San Carlos
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Read the Full Video Transcript
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center. I'm delighted to be joined today on UroToday by Dr. Javier Puente, who is a medical oncologist in Madrid, Spain. Today we're going to be discussing his GU ASCO 2025 presentation, looking at the PARASEC trial. And we'll get into the details of that. Javier, thanks so much for joining us.
Javier Puente: Hi, it's my pleasure. Thanks.
Zachary Klaassen: Awesome. So just by way of background, before we get into PARASEC—I know you're going to go through that—but just give us a high-level overview of the ARAMIS trial, which was looking at darolutamide plus ADT versus ADT alone in M0 CRPC and how PARASEC came about from the ARAMIS trial.
Javier Puente: Yes, Zach. Well, I think that the ARAMIS trial was a pivotal randomized, double blind, phase III study evaluating the activity of darolutamide versus placebo in patients with non-metastatic CRPC, who have a high risk to develop metastasis.
We know today that the primary endpoint of the ARAMIS study was achieved. Darolutamide significantly improved the metastasis-free survival by approximately 22 months compared to placebo with a hazard ratio that's very, very good. And also, this trial demonstrated an advantage in overall survival, with a 31% of reduction in the risk of death with the use of darolutamide in this context that, in the past, we don't have any other alternatives of treatment.
And in terms of safety profile, darolutamide was a well-tolerated drug with a minimal impact in terms of quality of life. So behind this trial, in Spain, we have different alternatives of treatment for patients with metastatic CRPC. But we don't know what is the treatment patterns of those patients that have been included in these kind of trials, like the ARAMIS trials or with the SPARTAN trial. Patients that have been treated with a hormonal therapy in this context of the non-metastatic CRPC.
So we designed this study. This is a retrospective and observational, multicenter and longitudinal study in patients that have been included in the ARAMIS trial in Spain and have received darolutamide.
So if you want, we can show the trial design. And this is the poster and the study that has been presented during the ASCO GU 2025. And as I mentioned, this is a retrospective, observational, and multicenter longitudinal follow-up study, including patients that have been recruited in the ARAMIS trial in Spain and has been treated with darolutamide.
And we know that 117 patients were included in Spain. 75 of those patients were randomized to receive darolutamide. And 42 patients were randomized to receive placebo. And for those patients that have received placebo, 16 patients were crossed over to darolutamide. So at the end, we have 91 patients receiving darolutamide in these non-metastatic CRPC included in the ARAMIS study.
And at the end, we evaluated 85 of those 91—and these patients have been included in the study—and trying to recover all the information about the patterns of treatment where the patients have developed a metastatic CRPC. Summaries about the results, Zach, of this study. Obviously, this is real-world treatment patterns because the patients that have been treated with darolutamide in this setting, after that, they developed a metastatic CRPC. They were treated in all the treatments that have been available in Spain at this moment. So we have chemotherapy. We have radium 223. We have PARP inhibitors.
And interestingly, first, 29% of the patients that have received darolutamide didn't receive any treatment after progression to metastatic CRPC. So this is really interesting for our real-world data and for our patients.
Obviously, the median age during the inclusion in the ARAMIS trial is around 76 years old. So the patients are elderly in these situations. But interestingly, one third of the patients didn't receive any treatment when they are metastatic.
And among those treated, in first line, 63% received abiraterone as the first-line setting. And this is really interesting because in most of the guidelines today, they recommended to change the mechanism of actions and to move from a newer hormonal therapy to chemotherapy because the sequential hormones in Europe and in Spain. And it is not supported by the pharmacy department. But interestingly, in this trial, 63% of the patients that have received a first line after darolutamide received another hormone therapy like abiraterone.
And in second line, the percentage of patients that have been treated with chemotherapy is so high. We have 76% of all of them receive a chemotherapy—most of them, docetaxel; 20%, around that, cabazitaxel. So interestingly, again, this is a delay in the use of chemotherapy in this population. And finally, Zach, another important fact in this retrospective analysis is that only 20% of all the patients receive osteoclastic-targeted therapy, zoledronic or denosumab in this context. And I think that is really interesting for a realistic point of view in our daily clinical practice, Zach.
Zachary Klaassen: Yeah, great summary, Javier. And I think congratulations on setting this up because we often wonder, these big registration trials costing millions of dollars, what happens to these patients afterwards? So it's very intriguing to see a subset of these patients, seeing what happens to them afterwards. I think you brought up a couple good points. We saw abiraterone, as you mentioned, the most common first line after progression. But I think you nailed it. I think it's that patient that was 76 when they started the trial, maybe in their early 80s now. Any other insights into maybe why patients were getting abiraterone versus docetaxel?
Javier Puente: Yeah, interesting. We don't know why. Maybe—I have a suspicion of that, because this trial was performed in a majority of the centers by a PI of urologists, not a medical oncologist, Zach. So I believe that most of them are treated by urologists. And maybe in a conversation with the patients, when the patients suffer a metastatic CRPC, most of them will progress in an asymptomatic way with low to moderate disease. And maybe these kind of situations could move to the urologist to prescribe a second hormone therapy before using chemotherapy, Zach.
Zachary Klaassen: Yeah, great point. The other one, I think, the 20% utilization of bone-protective agents is very interesting because we've seen with ERA 223 and then we've seen with PEACE-3 the importance. And Fred Saad has been really hammering home bone-protective agents for years now. But certainly, this probably reflects real-world outcomes, and not just Spain but probably across many countries. Any thoughts about why the utilization is so low in these mCRPC patients?
Javier Puente: Yeah, I think that first, I think that we have a lot of active drugs, Zach, in this context. And maybe the health care professional thinks that it is enough to prescribe an inactive drug to avoid these events, skeletal events, in the future of those patients. But this is a mistake. I think that most of these drugs could be combined perfectly with this kind of drug, like denosumab or zoledronic acid, to reduce these escalated adverse events.
And I think that obviously in this context, this data reflects the real situation right now, even in the medical oncology perspective, because we think that we will prescribe a chemotherapy or we'll prescribe a hormonal therapy, and it is not necessary to prescribe any other things. And this is a mistake, I think so, yeah.
Zachary Klaassen: Yeah, great point. It's been a great discussion. Congratulations on the work, again.
Javier Puente: Oh, thank you.
Zachary Klaassen: Maybe a couple of take-home messages for our UroToday listeners.
Javier Puente: Yeah, well, I think that, first, in this post-darolutamide treatment in metastatic CRPC, we have observed that this is a very heterogeneous situation in the real-world data, at least in Spain. And nearly one third of the patients didn't receive any treatment after progression.
Secondly, I think that the guidelines discordant in practice are very common, I think so. And the underutilization of the osteoclastic therapy, that it is critical for the bone health and the quality of life, is a reflex of this discordant practice nowadays. I think that it is clear that we need to establish more standardized, evidence-based treatment algorithms across the country.
We have guidelines, Zach. We have many meetings. But we need to continue the medical education to select the best treatment sequencing and the use of these bone-targeting agents. And finally, obviously, I think that the clinicians—urologists, medical oncologists, radiation oncologists—need to prioritize this health bone in the future of these kind of patients, Zach.
Zachary Klaassen: Well said. Javier, thanks so much for your time and expertise on UroToday and for joining us.
Javier Puente: Thank you very much, Zach.
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center. I'm delighted to be joined today on UroToday by Dr. Javier Puente, who is a medical oncologist in Madrid, Spain. Today we're going to be discussing his GU ASCO 2025 presentation, looking at the PARASEC trial. And we'll get into the details of that. Javier, thanks so much for joining us.
Javier Puente: Hi, it's my pleasure. Thanks.
Zachary Klaassen: Awesome. So just by way of background, before we get into PARASEC—I know you're going to go through that—but just give us a high-level overview of the ARAMIS trial, which was looking at darolutamide plus ADT versus ADT alone in M0 CRPC and how PARASEC came about from the ARAMIS trial.
Javier Puente: Yes, Zach. Well, I think that the ARAMIS trial was a pivotal randomized, double blind, phase III study evaluating the activity of darolutamide versus placebo in patients with non-metastatic CRPC, who have a high risk to develop metastasis.
We know today that the primary endpoint of the ARAMIS study was achieved. Darolutamide significantly improved the metastasis-free survival by approximately 22 months compared to placebo with a hazard ratio that's very, very good. And also, this trial demonstrated an advantage in overall survival, with a 31% of reduction in the risk of death with the use of darolutamide in this context that, in the past, we don't have any other alternatives of treatment.
And in terms of safety profile, darolutamide was a well-tolerated drug with a minimal impact in terms of quality of life. So behind this trial, in Spain, we have different alternatives of treatment for patients with metastatic CRPC. But we don't know what is the treatment patterns of those patients that have been included in these kind of trials, like the ARAMIS trials or with the SPARTAN trial. Patients that have been treated with a hormonal therapy in this context of the non-metastatic CRPC.
So we designed this study. This is a retrospective and observational, multicenter and longitudinal study in patients that have been included in the ARAMIS trial in Spain and have received darolutamide.
So if you want, we can show the trial design. And this is the poster and the study that has been presented during the ASCO GU 2025. And as I mentioned, this is a retrospective, observational, and multicenter longitudinal follow-up study, including patients that have been recruited in the ARAMIS trial in Spain and has been treated with darolutamide.
And we know that 117 patients were included in Spain. 75 of those patients were randomized to receive darolutamide. And 42 patients were randomized to receive placebo. And for those patients that have received placebo, 16 patients were crossed over to darolutamide. So at the end, we have 91 patients receiving darolutamide in these non-metastatic CRPC included in the ARAMIS study.
And at the end, we evaluated 85 of those 91—and these patients have been included in the study—and trying to recover all the information about the patterns of treatment where the patients have developed a metastatic CRPC. Summaries about the results, Zach, of this study. Obviously, this is real-world treatment patterns because the patients that have been treated with darolutamide in this setting, after that, they developed a metastatic CRPC. They were treated in all the treatments that have been available in Spain at this moment. So we have chemotherapy. We have radium 223. We have PARP inhibitors.
And interestingly, first, 29% of the patients that have received darolutamide didn't receive any treatment after progression to metastatic CRPC. So this is really interesting for our real-world data and for our patients.
Obviously, the median age during the inclusion in the ARAMIS trial is around 76 years old. So the patients are elderly in these situations. But interestingly, one third of the patients didn't receive any treatment when they are metastatic.
And among those treated, in first line, 63% received abiraterone as the first-line setting. And this is really interesting because in most of the guidelines today, they recommended to change the mechanism of actions and to move from a newer hormonal therapy to chemotherapy because the sequential hormones in Europe and in Spain. And it is not supported by the pharmacy department. But interestingly, in this trial, 63% of the patients that have received a first line after darolutamide received another hormone therapy like abiraterone.
And in second line, the percentage of patients that have been treated with chemotherapy is so high. We have 76% of all of them receive a chemotherapy—most of them, docetaxel; 20%, around that, cabazitaxel. So interestingly, again, this is a delay in the use of chemotherapy in this population. And finally, Zach, another important fact in this retrospective analysis is that only 20% of all the patients receive osteoclastic-targeted therapy, zoledronic or denosumab in this context. And I think that is really interesting for a realistic point of view in our daily clinical practice, Zach.
Zachary Klaassen: Yeah, great summary, Javier. And I think congratulations on setting this up because we often wonder, these big registration trials costing millions of dollars, what happens to these patients afterwards? So it's very intriguing to see a subset of these patients, seeing what happens to them afterwards. I think you brought up a couple good points. We saw abiraterone, as you mentioned, the most common first line after progression. But I think you nailed it. I think it's that patient that was 76 when they started the trial, maybe in their early 80s now. Any other insights into maybe why patients were getting abiraterone versus docetaxel?
Javier Puente: Yeah, interesting. We don't know why. Maybe—I have a suspicion of that, because this trial was performed in a majority of the centers by a PI of urologists, not a medical oncologist, Zach. So I believe that most of them are treated by urologists. And maybe in a conversation with the patients, when the patients suffer a metastatic CRPC, most of them will progress in an asymptomatic way with low to moderate disease. And maybe these kind of situations could move to the urologist to prescribe a second hormone therapy before using chemotherapy, Zach.
Zachary Klaassen: Yeah, great point. The other one, I think, the 20% utilization of bone-protective agents is very interesting because we've seen with ERA 223 and then we've seen with PEACE-3 the importance. And Fred Saad has been really hammering home bone-protective agents for years now. But certainly, this probably reflects real-world outcomes, and not just Spain but probably across many countries. Any thoughts about why the utilization is so low in these mCRPC patients?
Javier Puente: Yeah, I think that first, I think that we have a lot of active drugs, Zach, in this context. And maybe the health care professional thinks that it is enough to prescribe an inactive drug to avoid these events, skeletal events, in the future of those patients. But this is a mistake. I think that most of these drugs could be combined perfectly with this kind of drug, like denosumab or zoledronic acid, to reduce these escalated adverse events.
And I think that obviously in this context, this data reflects the real situation right now, even in the medical oncology perspective, because we think that we will prescribe a chemotherapy or we'll prescribe a hormonal therapy, and it is not necessary to prescribe any other things. And this is a mistake, I think so, yeah.
Zachary Klaassen: Yeah, great point. It's been a great discussion. Congratulations on the work, again.
Javier Puente: Oh, thank you.
Zachary Klaassen: Maybe a couple of take-home messages for our UroToday listeners.
Javier Puente: Yeah, well, I think that, first, in this post-darolutamide treatment in metastatic CRPC, we have observed that this is a very heterogeneous situation in the real-world data, at least in Spain. And nearly one third of the patients didn't receive any treatment after progression.
Secondly, I think that the guidelines discordant in practice are very common, I think so. And the underutilization of the osteoclastic therapy, that it is critical for the bone health and the quality of life, is a reflex of this discordant practice nowadays. I think that it is clear that we need to establish more standardized, evidence-based treatment algorithms across the country.
We have guidelines, Zach. We have many meetings. But we need to continue the medical education to select the best treatment sequencing and the use of these bone-targeting agents. And finally, obviously, I think that the clinicians—urologists, medical oncologists, radiation oncologists—need to prioritize this health bone in the future of these kind of patients, Zach.
Zachary Klaassen: Well said. Javier, thanks so much for your time and expertise on UroToday and for joining us.
Javier Puente: Thank you very much, Zach.