OASIS Project Highlights the Survival Benefits of Rapid PSA Decline with Apalutamide in Prostate Cancer - Benjamin Maughan
June 12, 2024
Zach Klaassen and Benjamin Maughan discuss new insights into the real-world application of apalutamide in treating metastatic hormone-sensitive prostate cancer (mHSPC). Dr. Maughan highlights the significance of achieving deep PSA responses as a key prognostic marker for patient outcomes. The OASIS project, utilizing data from diverse medical settings across the U.S., demonstrates that patients who achieve undetectable PSA levels within three months of treatment with ADT plus apalutamide have significantly improved survival rates, mirroring results from the TITAN trial. This real-world validation underscores the importance of intensified combination therapies in extending survival and improving quality of life for patients. Dr. Maughan emphasizes that deep PSA responses provide crucial insights for patient counseling and future clinical research, guiding better management strategies and the development of next-generation treatment options.
Biographies:
Benjamin Maughan, MD, PharmD, Assistant Professor, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Well Star MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Benjamin Maughan, MD, PharmD, Assistant Professor, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Well Star MCG, Georgia Cancer Center, Augusta, GA
Read the Full Video Transcript
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist in Augusta, Georgia. We are in Chicago for ASCO 2024. I'm delighted to be joined today by Dr. Ben Maughan, who is a GU Medical Oncologist at the Huntsman Cancer Institute. Ben, thanks so much for joining us.
Benjamin Maughan: Well, thank you for the opportunity to sit down and visit with you. This is wonderful.
Zachary Klaassen: Absolutely. So we're going to talk about some great data you presented at ASCO this weekend, really looking at real-world utilization of apalutamide and focusing on these really deep PSA responses. Before we get into that, maybe just tell us what the importance of a really deep PSA response is for our patients.
Benjamin Maughan: There's, I think, a twofold importance. One, the clinical practice implication and how does that play into prognosticating an individual patient's outcome. And then for the research aspect, it's a very important way to build our next generation of clinical trials and hopefully practice improvement. And this, it turns out, I think is a very powerful tool to accomplish both of these things.
Zachary Klaassen: That's great. So we know that TITAN, which was the registration trial, looked at apalutamide plus ADT in metastatic hormone-sensitive prostate cancer. Just walk us through the results where they did a similar analysis in that trial, correct?
Benjamin Maughan: Yeah. So this project that we're talking about today was a real-world application to really validate how meaningful these prospective clinical trial results are to the everyday patient that you and I see in clinic all the time. The TITAN trial is what preceded it. It was the registrational trial comparing ADT plus placebo versus ADT plus apalutamide. Along with a number of preceding registrational trials, all demonstrated that, similar to those, this intensified combination therapy significantly improved quality of life metrics, overall survival, and PSA responses. Patients just did better in every domain with intensified therapy compared to ADT monotherapy.
Zachary Klaassen: And so leading into the OASIS project. So just take us through what exactly it is, how many institutions, and what type of institutions make up this project?
Benjamin Maughan: This utilized the ConcertAI real-world data set. So this incorporated data from a myriad of predominantly medical oncology clinics across the United States. This was not a retrospective collection of a few limited academic medical centers. It reflected urology practices, some medical oncology clinics in the community, and academic medical oncology clinics, so quite a variety of places. We were able to do a number of different things with this. What we are presenting at this meeting was sort of like step two. What we previously published and presented in step one was similar to all these prospective trials comparing combination therapy versus monotherapy, demonstrating that all of these combinations using ADT plus whatever novel hormonal therapy of choice was superior to ADT monotherapy.
Zachary Klaassen: I see.
Benjamin Maughan: What we are trying to do with this second analysis was we picked one of the combinations. So in this case, ADT plus apalutamide, and we were really investigating the PSA metrics. In all of these preceding randomized phase three studies like TITAN, ARCHES, ENZAMET, LATITUDE, and others, we have observed that significant PSA responses at time point X—some studies use seven months, some use three months—but obtaining a very deep PSA response, an undetectable PSA, is strongly prognostic for overall survival in these clinical trial patients. So in this second phase of the OASIS project, we were trying to replicate that in real-world patients.
Zachary Klaassen: That's great. So maybe walk our listeners through the study design, how many patients, and some of the key results that you found?
Benjamin Maughan: The OASIS project included a large population of patients, about 3000. These were all patients with metastatic hormone-sensitive prostate cancer starting on ADT monotherapy or some ADT doublet. There was a limited number of patients treated with triplet therapy, ADT plus docetaxel plus darolutamide or ADT plus docetaxel and abiraterone. We didn't include those patients due to the very limited number. In the study that we presented, we selected those patients with ADT plus apalutamide or ADT alone. So it was a smaller subset, but in the apalutamide combination, we had almost 200 patients.
Zachary Klaassen: Good.
Benjamin Maughan: So a fairly reasonable sample size. And then again, we looked at those patients and broke them down into three cohorts: patients who, by three months, achieved an undetectable PSA (technically, our definition was a PSA of 0.2 or lower), patients who never achieved an undetectable PSA at any time point, and then the group in the middle who achieved an undetectable PSA but it took longer than three months.
Zachary Klaassen: I see.
Benjamin Maughan: And then we compared all of these different groups based on overall survival.
Zachary Klaassen: It's really quite remarkable. If you get your PSA down to undetectable in three months compared to those that didn't, those are really significant differences in survival. Maybe just walk us through those numbers.
Benjamin Maughan: So as you highlight, there's a dramatic difference. Never obtaining a PSA of an undetectable level was sort of the baseline or benchmark that we compared the other two cohorts against. For those patients who achieved a rapid and deep PSA response, defined as an undetectable PSA by three months or sooner, those patients had a hugely improved overall survival. The hazard ratio was less than 0.2, showing a phenomenal improvement in their prognosis. When you look at the overall survival data from the TITAN trial, these patients have an overall survival measured in eight-plus years. This specific group.
We don't have as long a follow-up with these patients in the OASIS study. So the best we can do is benchmark it against a two-year overall survival rate. The overall survival rate for this group that had an undetectable PSA by three months was approximately 90% at two years, which interestingly was identical to what we saw for a two-year overall survival rate in the TITAN trial for this exact same population that had an undetectable PSA by three months. In contrast, the patients who achieved an undetectable PSA at any time point but took longer than three months also had a significantly improved overall survival compared to the patients who never achieved an undetectable PSA. The hazard ratio was not as good, but it was still around 0.3.
Zachary Klaassen: Still excellent.
Benjamin Maughan: Excellent. Yes, yes. Excellent. So obtaining or not obtaining an undetectable PSA level is a pretty important marker for patients because that really helps me understand what their likely outcome is in terms of managing competing risks. How intensively should we be managing their cardiovascular health or how much should we be focusing on their bone health? For these patients, we have finally arrived at turning this disease into a chronic illness where we have to manage so many other things, even with our relatively limited number of treatment options today.
Zachary Klaassen: That's well said. And I think it's important to do these studies in the real world. In clinical trials, we're talking about hand-selected patients essentially, and really seeing if this still translates to the general urology clinic or oncology clinic. So to see those results line up with the registration trial is really important. And I think to your point about counseling patients, how do we talk to the patients about this? There are certainly things that we may tell them, but there are also things we're thinking about their disease process. If they're not achieving that PSA undetectable level, that's almost as significant as if they are. Correct?
Benjamin Maughan: Yeah, I think you highlighted it very nicely. Unfortunately, one finding that is pretty common is we see great results from registrational trials, and then a few years later when we finally start having some real-world data, we see that the results are still good. But there's often a step down, a decrement in the magnitude of the benefit we are offering patients. For a number of reasons, they may have more comorbidities, or maybe they have more aggressive disease in general. But strikingly, with this study, the real-world data was identical to what we see in the TITAN trial, which was very encouraging to me.
Because that influences how I counsel patients on these treatments. As I mentioned at the beginning, for me, there are really two domains that this is helpful for. One is the patient counseling piece, but the other is that it really influences how I and others are thinking about developing the next steps of research. Because exactly to your point, what do we do with that patient who doesn't achieve the undetectable PSA? There's definitely a lot of improvement needed in what we should be doing to help these patients. And right now we don't have a good answer other than I just need to make sure we're watching things closely. But it would be so much better to say, "Oh, this is not looking good. Let's take this next step to make things better." So these types of results really are helping to shape and inform the research arena that hopefully in the future will give us better options for these patients.
Zachary Klaassen: Excellent. It's been a great discussion. Maybe a couple of take-home points for our listeners regarding your work.
Benjamin Maughan: Yeah. First of all, intensified therapies offer tremendously better outcomes for patients, and almost exclusively every patient should be offered an intensified therapy. We're not there yet. There are still a lot of patients who are not getting intensified treatments. The second is that PSA is important, especially at this phase in their treatment. It's very prognostic. From my personal experience in counseling patients, achieving a rapid, deep PSA response can be a strong source of hope and optimism for the future. So I think it is important to keep this in mind as we're talking to patients.
Zachary Klaassen: Fantastic. Ben, thanks so much for joining us and for your time and expertise.
Benjamin Maughan: Well, thank you. It was wonderful being here and visiting with you as always.
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist in Augusta, Georgia. We are in Chicago for ASCO 2024. I'm delighted to be joined today by Dr. Ben Maughan, who is a GU Medical Oncologist at the Huntsman Cancer Institute. Ben, thanks so much for joining us.
Benjamin Maughan: Well, thank you for the opportunity to sit down and visit with you. This is wonderful.
Zachary Klaassen: Absolutely. So we're going to talk about some great data you presented at ASCO this weekend, really looking at real-world utilization of apalutamide and focusing on these really deep PSA responses. Before we get into that, maybe just tell us what the importance of a really deep PSA response is for our patients.
Benjamin Maughan: There's, I think, a twofold importance. One, the clinical practice implication and how does that play into prognosticating an individual patient's outcome. And then for the research aspect, it's a very important way to build our next generation of clinical trials and hopefully practice improvement. And this, it turns out, I think is a very powerful tool to accomplish both of these things.
Zachary Klaassen: That's great. So we know that TITAN, which was the registration trial, looked at apalutamide plus ADT in metastatic hormone-sensitive prostate cancer. Just walk us through the results where they did a similar analysis in that trial, correct?
Benjamin Maughan: Yeah. So this project that we're talking about today was a real-world application to really validate how meaningful these prospective clinical trial results are to the everyday patient that you and I see in clinic all the time. The TITAN trial is what preceded it. It was the registrational trial comparing ADT plus placebo versus ADT plus apalutamide. Along with a number of preceding registrational trials, all demonstrated that, similar to those, this intensified combination therapy significantly improved quality of life metrics, overall survival, and PSA responses. Patients just did better in every domain with intensified therapy compared to ADT monotherapy.
Zachary Klaassen: And so leading into the OASIS project. So just take us through what exactly it is, how many institutions, and what type of institutions make up this project?
Benjamin Maughan: This utilized the ConcertAI real-world data set. So this incorporated data from a myriad of predominantly medical oncology clinics across the United States. This was not a retrospective collection of a few limited academic medical centers. It reflected urology practices, some medical oncology clinics in the community, and academic medical oncology clinics, so quite a variety of places. We were able to do a number of different things with this. What we are presenting at this meeting was sort of like step two. What we previously published and presented in step one was similar to all these prospective trials comparing combination therapy versus monotherapy, demonstrating that all of these combinations using ADT plus whatever novel hormonal therapy of choice was superior to ADT monotherapy.
Zachary Klaassen: I see.
Benjamin Maughan: What we are trying to do with this second analysis was we picked one of the combinations. So in this case, ADT plus apalutamide, and we were really investigating the PSA metrics. In all of these preceding randomized phase three studies like TITAN, ARCHES, ENZAMET, LATITUDE, and others, we have observed that significant PSA responses at time point X—some studies use seven months, some use three months—but obtaining a very deep PSA response, an undetectable PSA, is strongly prognostic for overall survival in these clinical trial patients. So in this second phase of the OASIS project, we were trying to replicate that in real-world patients.
Zachary Klaassen: That's great. So maybe walk our listeners through the study design, how many patients, and some of the key results that you found?
Benjamin Maughan: The OASIS project included a large population of patients, about 3000. These were all patients with metastatic hormone-sensitive prostate cancer starting on ADT monotherapy or some ADT doublet. There was a limited number of patients treated with triplet therapy, ADT plus docetaxel plus darolutamide or ADT plus docetaxel and abiraterone. We didn't include those patients due to the very limited number. In the study that we presented, we selected those patients with ADT plus apalutamide or ADT alone. So it was a smaller subset, but in the apalutamide combination, we had almost 200 patients.
Zachary Klaassen: Good.
Benjamin Maughan: So a fairly reasonable sample size. And then again, we looked at those patients and broke them down into three cohorts: patients who, by three months, achieved an undetectable PSA (technically, our definition was a PSA of 0.2 or lower), patients who never achieved an undetectable PSA at any time point, and then the group in the middle who achieved an undetectable PSA but it took longer than three months.
Zachary Klaassen: I see.
Benjamin Maughan: And then we compared all of these different groups based on overall survival.
Zachary Klaassen: It's really quite remarkable. If you get your PSA down to undetectable in three months compared to those that didn't, those are really significant differences in survival. Maybe just walk us through those numbers.
Benjamin Maughan: So as you highlight, there's a dramatic difference. Never obtaining a PSA of an undetectable level was sort of the baseline or benchmark that we compared the other two cohorts against. For those patients who achieved a rapid and deep PSA response, defined as an undetectable PSA by three months or sooner, those patients had a hugely improved overall survival. The hazard ratio was less than 0.2, showing a phenomenal improvement in their prognosis. When you look at the overall survival data from the TITAN trial, these patients have an overall survival measured in eight-plus years. This specific group.
We don't have as long a follow-up with these patients in the OASIS study. So the best we can do is benchmark it against a two-year overall survival rate. The overall survival rate for this group that had an undetectable PSA by three months was approximately 90% at two years, which interestingly was identical to what we saw for a two-year overall survival rate in the TITAN trial for this exact same population that had an undetectable PSA by three months. In contrast, the patients who achieved an undetectable PSA at any time point but took longer than three months also had a significantly improved overall survival compared to the patients who never achieved an undetectable PSA. The hazard ratio was not as good, but it was still around 0.3.
Zachary Klaassen: Still excellent.
Benjamin Maughan: Excellent. Yes, yes. Excellent. So obtaining or not obtaining an undetectable PSA level is a pretty important marker for patients because that really helps me understand what their likely outcome is in terms of managing competing risks. How intensively should we be managing their cardiovascular health or how much should we be focusing on their bone health? For these patients, we have finally arrived at turning this disease into a chronic illness where we have to manage so many other things, even with our relatively limited number of treatment options today.
Zachary Klaassen: That's well said. And I think it's important to do these studies in the real world. In clinical trials, we're talking about hand-selected patients essentially, and really seeing if this still translates to the general urology clinic or oncology clinic. So to see those results line up with the registration trial is really important. And I think to your point about counseling patients, how do we talk to the patients about this? There are certainly things that we may tell them, but there are also things we're thinking about their disease process. If they're not achieving that PSA undetectable level, that's almost as significant as if they are. Correct?
Benjamin Maughan: Yeah, I think you highlighted it very nicely. Unfortunately, one finding that is pretty common is we see great results from registrational trials, and then a few years later when we finally start having some real-world data, we see that the results are still good. But there's often a step down, a decrement in the magnitude of the benefit we are offering patients. For a number of reasons, they may have more comorbidities, or maybe they have more aggressive disease in general. But strikingly, with this study, the real-world data was identical to what we see in the TITAN trial, which was very encouraging to me.
Because that influences how I counsel patients on these treatments. As I mentioned at the beginning, for me, there are really two domains that this is helpful for. One is the patient counseling piece, but the other is that it really influences how I and others are thinking about developing the next steps of research. Because exactly to your point, what do we do with that patient who doesn't achieve the undetectable PSA? There's definitely a lot of improvement needed in what we should be doing to help these patients. And right now we don't have a good answer other than I just need to make sure we're watching things closely. But it would be so much better to say, "Oh, this is not looking good. Let's take this next step to make things better." So these types of results really are helping to shape and inform the research arena that hopefully in the future will give us better options for these patients.
Zachary Klaassen: Excellent. It's been a great discussion. Maybe a couple of take-home points for our listeners regarding your work.
Benjamin Maughan: Yeah. First of all, intensified therapies offer tremendously better outcomes for patients, and almost exclusively every patient should be offered an intensified therapy. We're not there yet. There are still a lot of patients who are not getting intensified treatments. The second is that PSA is important, especially at this phase in their treatment. It's very prognostic. From my personal experience in counseling patients, achieving a rapid, deep PSA response can be a strong source of hope and optimism for the future. So I think it is important to keep this in mind as we're talking to patients.
Zachary Klaassen: Fantastic. Ben, thanks so much for joining us and for your time and expertise.
Benjamin Maughan: Well, thank you. It was wonderful being here and visiting with you as always.