Beyond Medical Advancements: Addressing Financial and Personal Challenges in Metastatic Castration-Sensitive Prostate Cancer Treatment - Neeraj Agarwal
June 14, 2023
Neeraj Agarwal articulates his vision for the future of treating metastatic castration-sensitive prostate cancer (CSPC). Agarwal delves into the remarkable therapeutic advancements in the past decade, notably, the shift to doublet and triplet therapies. Despite these developments, he draws attention to the underutilization of such treatments in real-world settings due to various barriers. Primarily, these include lack of data awareness among physicians, financial constraints, and patient concerns about side effects and maintaining their quality of life. Agarwal acknowledges that treatment costs rise significantly when moving from ADT monotherapy to doublet or triplet therapies, adding to the patient's burdens. Looking forward, he hopes for a more biomarker-based decision-making process, allowing for personalized treatments that patients can afford while maintaining their quality of life.
Biographies:
Neeraj Agarwal, MD, Professor, Presidential Endowed Chair of Cancer Research, Director GU Program, and the Center of Investigational Therapeutics (CIT) at the Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, MA
Biographies:
Neeraj Agarwal, MD, Professor, Presidential Endowed Chair of Cancer Research, Director GU Program, and the Center of Investigational Therapeutics (CIT) at the Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, MA
Read the Full Video Transcript
Alicia Morgans: Hi, I'm so thrilled to be here today with Professor Neeraj Agarwal, Professor of Medicine at the Huntsman Cancer Institute in Salt Lake City, Utah. Thank you so much for being here.
Neeraj Agarwal: Thank you for having me.
Alicia Morgans: Wonderful. So Neeraj, you gave a delightful program at ASCO, really talking about metastatic castration-sensitive prostate cancer, and the way that we need to think about that. Not only in the context of the therapies that we use, but in the context of the patient. Being at the center of clinical care and research, which, of course, is essentially, the theme of this year's ASCO. So can you tell me a little bit about it, please?
Neeraj Agarwal: I'm so glad ASCO leadership decided to have this theme this time for the ASCO 2023 annual meeting, which is patient as the center of care and research. And when I was asked to give this talk on treatment of metastatic castration-sensitive prostate cancer, I really wanted to keep that in mind, and wanted to make it a center point of my talk.
So yes, I did discuss the therapeutic advancements, which have been mind-boggling, in my view, in last decade. How things have changed in metastatic CSPC setting, in terms of therapy, with doublet therapies of androgen deprivation therapy plus androgen receptor pathway inhibitors.
I discussed how the hazard ratio for survival is so consistent among so many different trials, in the range of 30 to 35% reduction risk of death. Then I discussed about triplet therapy data, which we have seen in last two years, which compared the triplet therapy of ADT plus docetaxel, plus ARPI, with ADT plus docetaxel, but not with ADT plus ARPI.
And then again, showing advancements, improved survival benefits with triplet over ADT plus docetaxel. But then really, I want to bring attention to the fact, that despite all these advancements, multiple real world studies have consistently shown, majority of patients, until 2020, not receiving intensified antigen deprivation therapy. We are not even talking about triplets. Even doublet therapies, with highly well tolerated drugs, like ADT plus enzalutamide, abiraterone, apalutamide, they are not being used in the real world setting. And reason is why? Why is it happening?
So we went to into the studies, presented by Dr. Freedland, Dr. Dan George, very meaningful data out there, and my colleague, Dr. Umang Swami, in Huntsman Cancer Institute, we discussed. We looked at the real world use of ADT intensification therapy, and again, we saw, until as recent as 2020, a substantial number of patients are not getting therapy.
So next step was to look for why. And then, Dr. Freedland had this very nice study published, presented, where one of the top three concerns, or top three reasons for not utilizing intensified ADT in the metastatic CSPC setting, are number one, lack of awareness of data. So many physicians, our colleagues, are keeping the agents, forecast the resistance setting. They're saving them for a CRPC setting, because they see fantastic response in the PSA with ADT injection, which we know is going to happen.
But another most important reason, or reasons, were financial constraints, and then, concerns about how to handle those side effects among our patients. And then, patients' priorities. And in this context, I wanted to really highlight the study, reported by you and Dr. Laura Oswald, that patients actually have different priorities than what we like to think.
In your study, 32% patients clearly said, that they do not want to live longer no matter what. 20% patients said, they may not rely on their doctors strongly to tell them what to do. So patients, obviously, like quality of life to be maintained, and not quantity, or mere prolongation of life, may not be as important to our elderly patients who had a great life, for them, maintaining quality of life is as important.
Out-of-pocket cost, financially speaking, is a major player in our patient's mind. The cost of out-of-pocket cost goes up exponentially, from ADT monotherapy to ADT doublets or triplets. So that is another issue which is going on in our patient's mind. And then, I went on to talk about why this financial constraint are restricting our patients in one of the richest countries in the world. An out-of-pocket cost, copay accumulator program, and then, of course, the need for prior authorization of drugs.
These three factors are three of the top factors which are playing in our patient's mind, when they are making decisions for these more expensive therapies. And as we know, out-of-pocket cost may be tackled by legislation, by Inflation Reduction Act, but that will kick in 2025, and it will cap the out-of-pocket cost as $2,000 per year. And that is only for Medicare patients. But then, there are other issues, such as copay accumulator program, which do not allow our patients to use those financial assistance coupon towards their copay. That goes toward the base price of the drug. And I find it completely unacceptable. So there are bills which are pending in House and Senate, and I urged our audience to call their lawmakers to support these bills. And of course, there are many other factors.
But then, going back to the biomarkers I discussed about, can we customize these treatments? And there are multiple trials which are going on, which are looking at underlying biomarkers, such as homologous recombination repair positive mutation. If they are present in the tumor, patients are being enrolled in TALAPRO-3 trial and the AMPLITUDE trial. If they have PTEN deficient tumor, they're being enrolled in CAPItello trial. If they have PSM positivity on PSM PET scan, they are being recruited on the PSMAddition trial.
So my vision is, hopefully, we will have a more biomarker based decision making happening in metastatic castration-sensitive prostate cancer, and our patients will be able to afford those drugs, and will be able to maintain their quality of life.
Alicia Morgans: Absolutely. So balancing the realities of the system, and supporting our patients to get the treatment, combination treatments being really, the emphasis, and not perpetuating the disparities that leave some of our patients with ADT alone. Which again, is just as you said, no longer standard of care, not really the way that we want to go. Helping us overcome financial barriers, but also engaging with the patients, to ensure they have the quality of life that they want and deserve, and matching that right treatment to them. And of course, continuing the advocacy that ASCO has always been doing, to ensure that we have the policies in place to make this all possible. It's a wonderful vision for the future, and a wonderfully patient-centric approach to metastatic castration-resistant prostate cancer. I sincerely appreciate the education you always give us, and certainly, your time today.
Neeraj Agarwal: Thank you very much.
Alicia Morgans: Hi, I'm so thrilled to be here today with Professor Neeraj Agarwal, Professor of Medicine at the Huntsman Cancer Institute in Salt Lake City, Utah. Thank you so much for being here.
Neeraj Agarwal: Thank you for having me.
Alicia Morgans: Wonderful. So Neeraj, you gave a delightful program at ASCO, really talking about metastatic castration-sensitive prostate cancer, and the way that we need to think about that. Not only in the context of the therapies that we use, but in the context of the patient. Being at the center of clinical care and research, which, of course, is essentially, the theme of this year's ASCO. So can you tell me a little bit about it, please?
Neeraj Agarwal: I'm so glad ASCO leadership decided to have this theme this time for the ASCO 2023 annual meeting, which is patient as the center of care and research. And when I was asked to give this talk on treatment of metastatic castration-sensitive prostate cancer, I really wanted to keep that in mind, and wanted to make it a center point of my talk.
So yes, I did discuss the therapeutic advancements, which have been mind-boggling, in my view, in last decade. How things have changed in metastatic CSPC setting, in terms of therapy, with doublet therapies of androgen deprivation therapy plus androgen receptor pathway inhibitors.
I discussed how the hazard ratio for survival is so consistent among so many different trials, in the range of 30 to 35% reduction risk of death. Then I discussed about triplet therapy data, which we have seen in last two years, which compared the triplet therapy of ADT plus docetaxel, plus ARPI, with ADT plus docetaxel, but not with ADT plus ARPI.
And then again, showing advancements, improved survival benefits with triplet over ADT plus docetaxel. But then really, I want to bring attention to the fact, that despite all these advancements, multiple real world studies have consistently shown, majority of patients, until 2020, not receiving intensified antigen deprivation therapy. We are not even talking about triplets. Even doublet therapies, with highly well tolerated drugs, like ADT plus enzalutamide, abiraterone, apalutamide, they are not being used in the real world setting. And reason is why? Why is it happening?
So we went to into the studies, presented by Dr. Freedland, Dr. Dan George, very meaningful data out there, and my colleague, Dr. Umang Swami, in Huntsman Cancer Institute, we discussed. We looked at the real world use of ADT intensification therapy, and again, we saw, until as recent as 2020, a substantial number of patients are not getting therapy.
So next step was to look for why. And then, Dr. Freedland had this very nice study published, presented, where one of the top three concerns, or top three reasons for not utilizing intensified ADT in the metastatic CSPC setting, are number one, lack of awareness of data. So many physicians, our colleagues, are keeping the agents, forecast the resistance setting. They're saving them for a CRPC setting, because they see fantastic response in the PSA with ADT injection, which we know is going to happen.
But another most important reason, or reasons, were financial constraints, and then, concerns about how to handle those side effects among our patients. And then, patients' priorities. And in this context, I wanted to really highlight the study, reported by you and Dr. Laura Oswald, that patients actually have different priorities than what we like to think.
In your study, 32% patients clearly said, that they do not want to live longer no matter what. 20% patients said, they may not rely on their doctors strongly to tell them what to do. So patients, obviously, like quality of life to be maintained, and not quantity, or mere prolongation of life, may not be as important to our elderly patients who had a great life, for them, maintaining quality of life is as important.
Out-of-pocket cost, financially speaking, is a major player in our patient's mind. The cost of out-of-pocket cost goes up exponentially, from ADT monotherapy to ADT doublets or triplets. So that is another issue which is going on in our patient's mind. And then, I went on to talk about why this financial constraint are restricting our patients in one of the richest countries in the world. An out-of-pocket cost, copay accumulator program, and then, of course, the need for prior authorization of drugs.
These three factors are three of the top factors which are playing in our patient's mind, when they are making decisions for these more expensive therapies. And as we know, out-of-pocket cost may be tackled by legislation, by Inflation Reduction Act, but that will kick in 2025, and it will cap the out-of-pocket cost as $2,000 per year. And that is only for Medicare patients. But then, there are other issues, such as copay accumulator program, which do not allow our patients to use those financial assistance coupon towards their copay. That goes toward the base price of the drug. And I find it completely unacceptable. So there are bills which are pending in House and Senate, and I urged our audience to call their lawmakers to support these bills. And of course, there are many other factors.
But then, going back to the biomarkers I discussed about, can we customize these treatments? And there are multiple trials which are going on, which are looking at underlying biomarkers, such as homologous recombination repair positive mutation. If they are present in the tumor, patients are being enrolled in TALAPRO-3 trial and the AMPLITUDE trial. If they have PTEN deficient tumor, they're being enrolled in CAPItello trial. If they have PSM positivity on PSM PET scan, they are being recruited on the PSMAddition trial.
So my vision is, hopefully, we will have a more biomarker based decision making happening in metastatic castration-sensitive prostate cancer, and our patients will be able to afford those drugs, and will be able to maintain their quality of life.
Alicia Morgans: Absolutely. So balancing the realities of the system, and supporting our patients to get the treatment, combination treatments being really, the emphasis, and not perpetuating the disparities that leave some of our patients with ADT alone. Which again, is just as you said, no longer standard of care, not really the way that we want to go. Helping us overcome financial barriers, but also engaging with the patients, to ensure they have the quality of life that they want and deserve, and matching that right treatment to them. And of course, continuing the advocacy that ASCO has always been doing, to ensure that we have the policies in place to make this all possible. It's a wonderful vision for the future, and a wonderfully patient-centric approach to metastatic castration-resistant prostate cancer. I sincerely appreciate the education you always give us, and certainly, your time today.
Neeraj Agarwal: Thank you very much.