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Sequencing in Nonmetastatic and Metastatic CRPC

Panelists: Judd Moul, MD, Duke Cancer Institute; Neeraj Agarwal, MD, Hunstman Cancer Institute; Tanya Dorff, MD, City of Hope National Medical Center; Alicia Morgans, MD, PhD, Northwestern University Feinberg School of Medicine
Published: Thursday, Sep 12, 2019



Transcript: 

Tanya Dorff, MD:
Can I make a point?

Judd Moul, MD: Of course.

Tanya Dorff, MD: You were asking where we sequence in radium-223. I think of it like this. You have your ENZA [enzalutamide] and ABI [abiraterone] that work on androgen receptors. Then, you have your chemotherapy and radium-223 that do not. I think Alicia alluded to this earlier. When sequencing, it’s nice to go to something that works differently. That’s how I think about it, and you have to look at where the patient’s disease is, so imaging is important here. You want to make sure there is not a lot of active nodal disease, which can become problematic with hydronephrosis and those types of problems, or visceral involvement, if you’re going to choose the radium.

I wanted to raise the point that sipuleucel-T [SIP-T] does have a role. Sometimes we have someone who’s progressing from abiraterone or enzalutamide and they are totally asymptomatic. I’m not necessarily ready to jump to chemotherapy in that patient, and radium was really intended for symptomatic bony disease. You don’t have to have pain, but there has to be some activity there.

I think sipuleucel-T can be a nice option. It prolongs survival, and we’re trying to sequence our therapies to maximize our patients’ longevity. It’s also minimally toxic.

Alicia Morgans, MD, MPH: I 100% agree.

Judd Moul, MD: I’m so glad you brought up sipuleucel-T. We certainly wouldn’t want to exclude that from a discussion. With regard to more recent add-on SIP-T [sipuleucel-T], we have the PROCEED registry. One of my partners, Andy Armstrong MD at Duke Cancer Institute, has been heavily involved with the PROCEED registry. Our institution has been a fan of using Provenge or sipuleucel-T. From an educational standpoint, sipuleucel-T is FDA-approved for metastatic castration-resistant prostate cancer [mCRPC] that’s either minimally symptomatic or asymptomatic.

If patients have already progressed to narcotics for bone pain, for example, they are no longer eligible for sipuleucel-T. One of the things I worry about is, now that we have apalutamide and enzalutamide, and soon, darolutamide, in the M0 space, those drugs are going to be used before a patient becomes eligible for sipuleucel-T. Should we try to sequence that in before anything else?

I’ve talked to some urologists, and this is an interesting concept. They’ll have a patient with M0 CRPC that they will treat with enzalutamide or apalutamide. Then, say the patient goes on for 12 or 15 months. At about a year, they’re doing the newfangled PET [positron emission tomography] scan with the rationale of trying to find that early metastatic disease so that patients are “on label” for Provenge before they miss that opportunity.

It’s an interesting concept. That is perhaps a different variety of metastatic disease than is seen with traditional imaging. Alicia, can you comment on this intriguing data about African-American men treated with sipuleucel-T? Also, going back to the quartile data, it’s been said that we should use it in those with a lower PSA [prostate-specific antigen]. Maybe you can make a comment on that.

Alicia Morgans, MD, MPH: I was wondering if the quartile data are what’s driving the urologists’ actions. What the quartile data suggest is that the lower your PSA is, the more robust the response to sipuleucel-T, or the longer the survival benefit, would be. When you have some disease, but not a lot of disease, that’s where I envision sipuleucel-T being most helpful. There are enough cells around to allow the sipuleucel-T to get educated against those cells, attack them, and eradicate as much as they possibly can, but not so much that there’s no way that the immune response is going to be able to make a dent in that overwhelming burden of disease. I think it’s an interesting approach that the urologists are using. I wonder. I bet that the quartile data may be driving some of that.

What I also think is fascinating is that some of the PROCEED registry data suggest that African-American men have a much more robust response, or a longer survival in response to sipuleucel-T than Caucasian men. Whether that’s ultimately the truth, it’s incredibly compelling. If we can get treatment to the array of patients that we see and break down barriers in access, we can make a difference, even when we believe and have data to suggest that prostate cancer in African-American men is a higher cause of mortality and potentially, a more aggressive phenotype.

Judd Moul, MD: The signal in the PROCEED registry that African-American patients may do better prompted Susan Halabi PhD at our institution to look at a bunch of trials for CRPC [castration-resistant prostate cancer]. They seem to suggest that African-American men with mCRPC do better in general. That opens up a whole new avenue for research, which we certainly don’t have time to discuss, but it’s interesting.

Alicia Morgans, MD, MPH: Yes.

Judd Moul, MD: Final word on Provenge. Neeraj, I know you have not been using the drug, so just give me a devil’s advocate perspective.

Neeraj Agarwal, MD: I’m not saying I’m not using it. I’m not for or against any drug. I just think that in the type of practice we have, where patients are getting treated with upfront, intensified therapy that they never got in the past, they’re now progressing to castration-resistant metastatic prostate cancer. I think the disease biology is different, the disease volume is higher, and the disease aggressiveness is higher. This is a difference between my practice and your practice, Judd. Urologists are seeing M0 CRPC. We’re not seeing as many M0 CRPCs.

On the other hand, we are seeing de novo metastatic prostate cancer patients way more than urologists. We are treating them with upfront intensification. With each passing month, we have lower numbers of patients who would be eligible for sipuleucel-T. Because of the way this biology behaves, after being on this upfront, intensified therapy for 3 years, it’s different CRPC from what they used to have after being on Lupron for 16 months.

Judd Moul, MD: Your point is well-taken. The original data with [sipuleucel-T] was in the pre-novel oral therapy era. It’s complete speculation whether it’s going to provide a survival benefit in the setting after they’ve been on [abiraterone] or [enzalutamide].


Transcript Edited for Clarity 

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Transcript: 

Tanya Dorff, MD:
Can I make a point?

Judd Moul, MD: Of course.

Tanya Dorff, MD: You were asking where we sequence in radium-223. I think of it like this. You have your ENZA [enzalutamide] and ABI [abiraterone] that work on androgen receptors. Then, you have your chemotherapy and radium-223 that do not. I think Alicia alluded to this earlier. When sequencing, it’s nice to go to something that works differently. That’s how I think about it, and you have to look at where the patient’s disease is, so imaging is important here. You want to make sure there is not a lot of active nodal disease, which can become problematic with hydronephrosis and those types of problems, or visceral involvement, if you’re going to choose the radium.

I wanted to raise the point that sipuleucel-T [SIP-T] does have a role. Sometimes we have someone who’s progressing from abiraterone or enzalutamide and they are totally asymptomatic. I’m not necessarily ready to jump to chemotherapy in that patient, and radium was really intended for symptomatic bony disease. You don’t have to have pain, but there has to be some activity there.

I think sipuleucel-T can be a nice option. It prolongs survival, and we’re trying to sequence our therapies to maximize our patients’ longevity. It’s also minimally toxic.

Alicia Morgans, MD, MPH: I 100% agree.

Judd Moul, MD: I’m so glad you brought up sipuleucel-T. We certainly wouldn’t want to exclude that from a discussion. With regard to more recent add-on SIP-T [sipuleucel-T], we have the PROCEED registry. One of my partners, Andy Armstrong MD at Duke Cancer Institute, has been heavily involved with the PROCEED registry. Our institution has been a fan of using Provenge or sipuleucel-T. From an educational standpoint, sipuleucel-T is FDA-approved for metastatic castration-resistant prostate cancer [mCRPC] that’s either minimally symptomatic or asymptomatic.

If patients have already progressed to narcotics for bone pain, for example, they are no longer eligible for sipuleucel-T. One of the things I worry about is, now that we have apalutamide and enzalutamide, and soon, darolutamide, in the M0 space, those drugs are going to be used before a patient becomes eligible for sipuleucel-T. Should we try to sequence that in before anything else?

I’ve talked to some urologists, and this is an interesting concept. They’ll have a patient with M0 CRPC that they will treat with enzalutamide or apalutamide. Then, say the patient goes on for 12 or 15 months. At about a year, they’re doing the newfangled PET [positron emission tomography] scan with the rationale of trying to find that early metastatic disease so that patients are “on label” for Provenge before they miss that opportunity.

It’s an interesting concept. That is perhaps a different variety of metastatic disease than is seen with traditional imaging. Alicia, can you comment on this intriguing data about African-American men treated with sipuleucel-T? Also, going back to the quartile data, it’s been said that we should use it in those with a lower PSA [prostate-specific antigen]. Maybe you can make a comment on that.

Alicia Morgans, MD, MPH: I was wondering if the quartile data are what’s driving the urologists’ actions. What the quartile data suggest is that the lower your PSA is, the more robust the response to sipuleucel-T, or the longer the survival benefit, would be. When you have some disease, but not a lot of disease, that’s where I envision sipuleucel-T being most helpful. There are enough cells around to allow the sipuleucel-T to get educated against those cells, attack them, and eradicate as much as they possibly can, but not so much that there’s no way that the immune response is going to be able to make a dent in that overwhelming burden of disease. I think it’s an interesting approach that the urologists are using. I wonder. I bet that the quartile data may be driving some of that.

What I also think is fascinating is that some of the PROCEED registry data suggest that African-American men have a much more robust response, or a longer survival in response to sipuleucel-T than Caucasian men. Whether that’s ultimately the truth, it’s incredibly compelling. If we can get treatment to the array of patients that we see and break down barriers in access, we can make a difference, even when we believe and have data to suggest that prostate cancer in African-American men is a higher cause of mortality and potentially, a more aggressive phenotype.

Judd Moul, MD: The signal in the PROCEED registry that African-American patients may do better prompted Susan Halabi PhD at our institution to look at a bunch of trials for CRPC [castration-resistant prostate cancer]. They seem to suggest that African-American men with mCRPC do better in general. That opens up a whole new avenue for research, which we certainly don’t have time to discuss, but it’s interesting.

Alicia Morgans, MD, MPH: Yes.

Judd Moul, MD: Final word on Provenge. Neeraj, I know you have not been using the drug, so just give me a devil’s advocate perspective.

Neeraj Agarwal, MD: I’m not saying I’m not using it. I’m not for or against any drug. I just think that in the type of practice we have, where patients are getting treated with upfront, intensified therapy that they never got in the past, they’re now progressing to castration-resistant metastatic prostate cancer. I think the disease biology is different, the disease volume is higher, and the disease aggressiveness is higher. This is a difference between my practice and your practice, Judd. Urologists are seeing M0 CRPC. We’re not seeing as many M0 CRPCs.

On the other hand, we are seeing de novo metastatic prostate cancer patients way more than urologists. We are treating them with upfront intensification. With each passing month, we have lower numbers of patients who would be eligible for sipuleucel-T. Because of the way this biology behaves, after being on this upfront, intensified therapy for 3 years, it’s different CRPC from what they used to have after being on Lupron for 16 months.

Judd Moul, MD: Your point is well-taken. The original data with [sipuleucel-T] was in the pre-novel oral therapy era. It’s complete speculation whether it’s going to provide a survival benefit in the setting after they’ve been on [abiraterone] or [enzalutamide].


Transcript Edited for Clarity 
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