Radiopharmaceuticals in Prostate Cancer: A Deep Dive into Patient-Reported Outcomes - Scott Tagawa
September 15, 2021
Alicia Morgans converses with Scott Tagawa about patient-reported outcomes in men undergoing PSMA targeted radiopharmaceutical treatments for prostate cancer. The discussion centers on a Department of Defense-funded study that aims to develop a new patient-reported outcome tool specifically for this patient population. Dr. Tagawa elaborates on the instruments commonly used in clinical trials, such as the Brief Pain Inventory Short Form and FACT-P, to assess patients' quality of life. Despite the occurrence of adverse events in nearly all study participants, the research finds that quality of life remains largely stable. Dr. Tagawa emphasizes the importance of patient-reported outcomes and suggests that the preservation of quality of life can occur even in the presence of adverse events, provided the treatment is effective.
Biographies:
Scott T. Tagawa, MD, Associate Professor of Clinical Medicine, Clinical Urology, Medical Director, Genitourinary Oncology Research Program, Weill Cornell Medicine, New York, NY
Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts.
Biographies:
Scott T. Tagawa, MD, Associate Professor of Clinical Medicine, Clinical Urology, Medical Director, Genitourinary Oncology Research Program, Weill Cornell Medicine, New York, NY
Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts.
Read the Full Video Transcript
Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist at the Dana Farber Cancer Institute in Boston. I'm so excited to have here with me today a good friend and colleague Dr. Scott Tagawa, who is a Professor of Medicine and Urology at Weill Cornell Medicine, as well as being an attending physician at New York-Presbyterian. Thank you so much for being here with me today, Dr. Tagawa.
Scott Tagawa: Thanks very much for the invitation.
Alicia Morgans: Wonderful. I wanted to talk with you a little bit about some patient-reported outcomes, and health-related quality of life assessments that you and the team at Moffitt have done to really investigate how patients who are receiving PSMA targeted radiopharmaceuticals are experiencing that treatment. Can you tell us a little bit about your partnership with this team and what you and the team investigated?
Scott Tagawa: Sure. This is a partnership that started because there were some ideas that were out there and a number of us from different institutions got together to have some conversations. This fortunately resulted in a collaborative Department of Defense Idea Award that is funding studies essentially looking at two things, a retrospective portion looking at patient-reported outcomes on prospective studies in men with prostate cancer receiving radionuclide therapy and then a prospective component looking to create a new patient reported outcome tool for this patient population.
Alicia Morgans: Fantastic. And I think that's so important because there are always needs to characterize different adverse events as new therapies come about and radiopharmaceuticals have not been specifically identified and assessed in these instruments. So really important work and really interesting. You and the team, I think were doing in this particular presentation from ESMO 2021, some of that initial retrospective work that you mentioned. Can you tell us a little bit about who the patients were and which instruments they were using to really report and characterize their quality of life?
Scott Tagawa: Sure. Within each one of our, at least more modern clinical trials, we've embedded patient-reported outcomes using different instruments. But what they have all had in common is the Brief Pain Inventory Short Form or BPI Short Form, as well as FACT-P, pre-treatment, and at 12 weeks, that's what they've all had in common. Some of the different studies also included other instruments and sometimes different time points but that is what they've all had in common. We have reported some of the individual study peer outcome data with those individual studies, but here what we've done is we've lumped basically two studies where patients were getting either lutetium PSMA-617, which is a beta emitter linked to a small molecule against PSMA. People might recognize that as the radionuclide used in the VISION study but the regimen that we used is a dose intense regimen. That is kind of one reason that we combined this together.
And the other is an antibody called J591, which recognizes the external domain of PSMA radiolabeled with actinium-225, which is an alpha emitter, which is much more potent, although shorter range. We decided, okay, these are all essentially more potent therapies because of the lutetium dosing schedule, which is a high dose over a short period of time, it would be reasonable to combine these. And then also known as you mentioned at the beginning, you like I, and I think a lot of the people recognize that patient-reported outcomes are very important because this is what we are doing. We are treating patients and we want their lives to be as good as possible. And that is despite the fact that essentially every single drug that we have that works has adverse event rates that it carries with it.
Alicia Morgans: Yeah, I agree. And I think from a patient perspective, as we are choosing these treatments, it's so helpful for them to have some characterization of what that experience is like, which is exactly what you and the team are doing. And I'm glad that you are doing it. And I wonder in this particular study, how did you find those measures, the FACT-P, and the pain index? Were these really severely impacted during the treatment with these radiopharmaceuticals? Or how did things end up?
Scott Tagawa: The bottom line is the preservation of patient-reported outcomes and quality of life. So despite that, approximately 95% of the subjects, the patients that had prostate cancer participating in these studies had adverse events, at least identified by the clinician. And we know that patient-reported adverse events might be slightly different than clinician-reported adverse events but virtually everyone had adverse events. As we know from the inhibitor studies, mostly grade one and grade two, aside from some hematolgic toxicity. But despite that, baseline and 12 weeks were basically the same regardless of the drug or the regimen that was used. That being said, there was also an interesting subset analysis. Luckily, most patients have some sort of disease control at least when you look at PSA, 70 plus percent will have at least some PSA decline, 1% or more.
We think that there is at least some control of that. But when we look at PSA responders or at least PSA that did go down to some degree versus those that didn't, then there was a difference. That small fraction, which in this dataset was about one in five, that had PSA go up as the best response, did have a decrease in FACT-P overall quality of life. Now, whether that is attributable to adverse events from the drug in the absence of a response or that was related to prostate cancer disease progression or some combination, we don't really know.
I do think that luckily, all of the drugs that we are generally talking about have success. I think that the adverse events of severity and rates are offset by disease control and we know that even with "cytotoxic chemotherapy," we know that when there is disease control, there can be an improvement or preservation in patient-reported outcomes, both in short and longer-term, depending on the patient population. We did look at the kind of disease control rate by PSA and that did look to be a little bit different, at least in terms of FACT-P.
Alicia Morgans: Well, I'm so glad that you and the team did that part of the analysis because the median levels of these patient-reported outcomes can be really similar sometimes between groups. But when you start looking at patients who are in the upper or lower quartile of quality of life, you can find these associations with disease progression or maybe superior disease control, depending on which quartile you're looking at. And it can be really, I think, additive in potentially prognosticating ultimately if we put together the right models, that combination of disease biomarker change and quality of life change. Really interesting that you are starting to get into this.
One other thing that I wanted to ask is that sometimes when scales look relatively unchanged, it's because there isn't a change in the patient's health-related quality of life. Sometimes when things look relatively unchanged, it's because we are not measuring or not sensitively measuring some of the things that a patient is experiencing. From your perspective and from the team's perspective, I think this might be part of what's prompting you to consider investigating whether there needs to be a specific radiopharmaceutical patient-reported outcome instrument that could help characterize things better. Did this study help inform you at all as you are thinking about moving into the next steps?
Scott Tagawa: We are looking at broader data sets with that. I would say that this specific analysis didn't change too much but that was mostly because I'm dealing with the patients on an individual basis all the time. And I know that at least in my mind that we will look at CTCAE and dry mouth or xerostomia. There are categories that are there but if anyone is looking at grade three, it's more or less, throw in the feeding tube, we say, and then grade two could be severe. There are many other ones that are kind of grade two that in my viewpoint can really affect patients' lives.
So I think we can do better than that. And I think no better source than getting the information from the patient themselves. I think with broader numbers, just this small group, there are other institutions and we are looking at datasets from another phase one, two, as well as phase three trials with radiopharmaceuticals. I think that we will be able to at least tweak what we have to improve things so we can get into some of those finite details that are a little bit more specific to radioisotope or radiopharmaceutical therapy.
Alicia Morgans: Great. I really do look forward to seeing your work and the team of course is a phenomenal one. Congratulations on the DOD funding for this team's efforts and certainly in completing this project. If you had to summarize this work from your ESMO presentation, what would that be?
Scott Tagawa: I would say that patient-reported outcomes are important. And despite the fact that there are real adverse events that we measure objectively and subjectively, I think in the setting of a good drug, that there can be the preservation of quality of life, despite adverse events with drugs.
Alicia Morgans: It is a great message and again, fantastic work. Thank you and the team very much for the work that you do, for the patients participating, and thank you for taking the time to speak with us about it today.
Scott Tagawa: Thank you very much.
Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist at the Dana Farber Cancer Institute in Boston. I'm so excited to have here with me today a good friend and colleague Dr. Scott Tagawa, who is a Professor of Medicine and Urology at Weill Cornell Medicine, as well as being an attending physician at New York-Presbyterian. Thank you so much for being here with me today, Dr. Tagawa.
Scott Tagawa: Thanks very much for the invitation.
Alicia Morgans: Wonderful. I wanted to talk with you a little bit about some patient-reported outcomes, and health-related quality of life assessments that you and the team at Moffitt have done to really investigate how patients who are receiving PSMA targeted radiopharmaceuticals are experiencing that treatment. Can you tell us a little bit about your partnership with this team and what you and the team investigated?
Scott Tagawa: Sure. This is a partnership that started because there were some ideas that were out there and a number of us from different institutions got together to have some conversations. This fortunately resulted in a collaborative Department of Defense Idea Award that is funding studies essentially looking at two things, a retrospective portion looking at patient-reported outcomes on prospective studies in men with prostate cancer receiving radionuclide therapy and then a prospective component looking to create a new patient reported outcome tool for this patient population.
Alicia Morgans: Fantastic. And I think that's so important because there are always needs to characterize different adverse events as new therapies come about and radiopharmaceuticals have not been specifically identified and assessed in these instruments. So really important work and really interesting. You and the team, I think were doing in this particular presentation from ESMO 2021, some of that initial retrospective work that you mentioned. Can you tell us a little bit about who the patients were and which instruments they were using to really report and characterize their quality of life?
Scott Tagawa: Sure. Within each one of our, at least more modern clinical trials, we've embedded patient-reported outcomes using different instruments. But what they have all had in common is the Brief Pain Inventory Short Form or BPI Short Form, as well as FACT-P, pre-treatment, and at 12 weeks, that's what they've all had in common. Some of the different studies also included other instruments and sometimes different time points but that is what they've all had in common. We have reported some of the individual study peer outcome data with those individual studies, but here what we've done is we've lumped basically two studies where patients were getting either lutetium PSMA-617, which is a beta emitter linked to a small molecule against PSMA. People might recognize that as the radionuclide used in the VISION study but the regimen that we used is a dose intense regimen. That is kind of one reason that we combined this together.
And the other is an antibody called J591, which recognizes the external domain of PSMA radiolabeled with actinium-225, which is an alpha emitter, which is much more potent, although shorter range. We decided, okay, these are all essentially more potent therapies because of the lutetium dosing schedule, which is a high dose over a short period of time, it would be reasonable to combine these. And then also known as you mentioned at the beginning, you like I, and I think a lot of the people recognize that patient-reported outcomes are very important because this is what we are doing. We are treating patients and we want their lives to be as good as possible. And that is despite the fact that essentially every single drug that we have that works has adverse event rates that it carries with it.
Alicia Morgans: Yeah, I agree. And I think from a patient perspective, as we are choosing these treatments, it's so helpful for them to have some characterization of what that experience is like, which is exactly what you and the team are doing. And I'm glad that you are doing it. And I wonder in this particular study, how did you find those measures, the FACT-P, and the pain index? Were these really severely impacted during the treatment with these radiopharmaceuticals? Or how did things end up?
Scott Tagawa: The bottom line is the preservation of patient-reported outcomes and quality of life. So despite that, approximately 95% of the subjects, the patients that had prostate cancer participating in these studies had adverse events, at least identified by the clinician. And we know that patient-reported adverse events might be slightly different than clinician-reported adverse events but virtually everyone had adverse events. As we know from the inhibitor studies, mostly grade one and grade two, aside from some hematolgic toxicity. But despite that, baseline and 12 weeks were basically the same regardless of the drug or the regimen that was used. That being said, there was also an interesting subset analysis. Luckily, most patients have some sort of disease control at least when you look at PSA, 70 plus percent will have at least some PSA decline, 1% or more.
We think that there is at least some control of that. But when we look at PSA responders or at least PSA that did go down to some degree versus those that didn't, then there was a difference. That small fraction, which in this dataset was about one in five, that had PSA go up as the best response, did have a decrease in FACT-P overall quality of life. Now, whether that is attributable to adverse events from the drug in the absence of a response or that was related to prostate cancer disease progression or some combination, we don't really know.
I do think that luckily, all of the drugs that we are generally talking about have success. I think that the adverse events of severity and rates are offset by disease control and we know that even with "cytotoxic chemotherapy," we know that when there is disease control, there can be an improvement or preservation in patient-reported outcomes, both in short and longer-term, depending on the patient population. We did look at the kind of disease control rate by PSA and that did look to be a little bit different, at least in terms of FACT-P.
Alicia Morgans: Well, I'm so glad that you and the team did that part of the analysis because the median levels of these patient-reported outcomes can be really similar sometimes between groups. But when you start looking at patients who are in the upper or lower quartile of quality of life, you can find these associations with disease progression or maybe superior disease control, depending on which quartile you're looking at. And it can be really, I think, additive in potentially prognosticating ultimately if we put together the right models, that combination of disease biomarker change and quality of life change. Really interesting that you are starting to get into this.
One other thing that I wanted to ask is that sometimes when scales look relatively unchanged, it's because there isn't a change in the patient's health-related quality of life. Sometimes when things look relatively unchanged, it's because we are not measuring or not sensitively measuring some of the things that a patient is experiencing. From your perspective and from the team's perspective, I think this might be part of what's prompting you to consider investigating whether there needs to be a specific radiopharmaceutical patient-reported outcome instrument that could help characterize things better. Did this study help inform you at all as you are thinking about moving into the next steps?
Scott Tagawa: We are looking at broader data sets with that. I would say that this specific analysis didn't change too much but that was mostly because I'm dealing with the patients on an individual basis all the time. And I know that at least in my mind that we will look at CTCAE and dry mouth or xerostomia. There are categories that are there but if anyone is looking at grade three, it's more or less, throw in the feeding tube, we say, and then grade two could be severe. There are many other ones that are kind of grade two that in my viewpoint can really affect patients' lives.
So I think we can do better than that. And I think no better source than getting the information from the patient themselves. I think with broader numbers, just this small group, there are other institutions and we are looking at datasets from another phase one, two, as well as phase three trials with radiopharmaceuticals. I think that we will be able to at least tweak what we have to improve things so we can get into some of those finite details that are a little bit more specific to radioisotope or radiopharmaceutical therapy.
Alicia Morgans: Great. I really do look forward to seeing your work and the team of course is a phenomenal one. Congratulations on the DOD funding for this team's efforts and certainly in completing this project. If you had to summarize this work from your ESMO presentation, what would that be?
Scott Tagawa: I would say that patient-reported outcomes are important. And despite the fact that there are real adverse events that we measure objectively and subjectively, I think in the setting of a good drug, that there can be the preservation of quality of life, despite adverse events with drugs.
Alicia Morgans: It is a great message and again, fantastic work. Thank you and the team very much for the work that you do, for the patients participating, and thank you for taking the time to speak with us about it today.
Scott Tagawa: Thank you very much.