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Nonmetastatic CRPC: The Changing Landscape of Treatment

Insights From: Julie Graff, MD, Oregon Health and Science University; Judd W. Moul, MD, Duke University Medical Center; Charles J. Ryan, MD, UCSF Helen Diller Comprehensive Cancer Center
Published: Tuesday, Jan 23, 2018



Transcript:

Judd W. Moul, MD: The future for nonmetastatic castration-resistant prostate cancer looks extremely bright in the sense that we’ve now gone through all of our careers, and those of us who treat prostate cancer every day have never had anything that we could specifically use for M0 CRPC. We’ve typically told the patients, “We’re just going to monitor you, we’ll wait until you develop metastasis, and then we’ll give you a novel agent.” We’re at the cusp of having 1 or multiple novel oral antiandrogens FDA approved specifically for M0 CRPC.

In the fall of 2017, both Janssen Pharmaceuticals and Pfizer Pharmaceuticals had press releases stating that their respective drugs, enzalutamide and apalutamide, are effective in M0 CRPC. This means that both drugs delayed the time to clinical metastasis in these patients without metastasis, meeting the primary endpoint of both phase III trials, SPARTAN and PROSPER. That means that in a matter of weeks or months, urologists and medical oncologists could have new treatments available that we’ve never had before for patients with M0 CRPC.

Julie Graff, MD: The landscape of treating nonmetastatic castration-resistant prostate cancer will change dramatically. In the past few decades, we’ve been tinkering with older drugs, some of which aren’t even approved in this setting, such as ketoconazole. It’s not even an FDA-approved agent in prostate cancer. We’re just hoping to get the PSA down and hoping to extend the time until metastases develop. With the advent of these second-generation AR-targeted agents, we will be using them sooner, for sure. What does that mean later on? So, if a patient’s cancer progresses on these agents, then he’s more likely to get chemotherapy and other drugs when the cancer becomes metastatic.

Charles J. Ryan, MD: Nonmetastatic castration-resistant prostate cancer is an interesting entity, because there are a couple of things that could happen. One is it could go away, because with novel imaging agents we might be able to detect metastases. And so, it could be that some of the patients who–5 years ago and even today–we think of as having nonmetastatic disease actually have metastatic disease, but we’re just not detecting it because we’re not using the most sophisticated imaging modality.

Over the course of the next few years, we’re going to see data on PSMA (prostate-specific membrane antigen)-PET scans and other types of new-generation imaging modalities that might tell us some of the patients who have nonmetastatic disease actually have metastatic disease. That’s number one. Number 2 is that the future for those patients who have slowly progressive nonmetastatic disease is that we will be able to preserve them into that nonmetastatic state with next-generation androgen receptor antagonists, most likely. It’s also possible that we’ll look at immunotherapies in this setting, but I really think that the future in the short run is with integrating newer AR-targeted agents into this group of patients.

The landscape for nonmetastatic castration-resistant prostate cancer is changing because we’ll likely have therapies in that space whereas previously, we really haven’t had anything. This has been an area that I actually think is about 25% of our castration-resistant patient population, at least it is in some estimates. This is an area where physicians like myself have been treating patients with off-label therapies. We haven’t had an on-label therapy in this group of patients. We’ve simply been observing them, waiting for them to develop metastatic disease. It has always felt a little unsatisfactory that we should have to wait for a complication or progression to occur before we intervene, when we know that therapies may be beneficial. So, I’m quite excited about the possibility of having a therapy that’s available for nonmetastatic disease because I can confidently tell patients that I’m going to have a significant chance to prevent metastasis from occurring.

Transcript Edited for Clarity 
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Transcript:

Judd W. Moul, MD: The future for nonmetastatic castration-resistant prostate cancer looks extremely bright in the sense that we’ve now gone through all of our careers, and those of us who treat prostate cancer every day have never had anything that we could specifically use for M0 CRPC. We’ve typically told the patients, “We’re just going to monitor you, we’ll wait until you develop metastasis, and then we’ll give you a novel agent.” We’re at the cusp of having 1 or multiple novel oral antiandrogens FDA approved specifically for M0 CRPC.

In the fall of 2017, both Janssen Pharmaceuticals and Pfizer Pharmaceuticals had press releases stating that their respective drugs, enzalutamide and apalutamide, are effective in M0 CRPC. This means that both drugs delayed the time to clinical metastasis in these patients without metastasis, meeting the primary endpoint of both phase III trials, SPARTAN and PROSPER. That means that in a matter of weeks or months, urologists and medical oncologists could have new treatments available that we’ve never had before for patients with M0 CRPC.

Julie Graff, MD: The landscape of treating nonmetastatic castration-resistant prostate cancer will change dramatically. In the past few decades, we’ve been tinkering with older drugs, some of which aren’t even approved in this setting, such as ketoconazole. It’s not even an FDA-approved agent in prostate cancer. We’re just hoping to get the PSA down and hoping to extend the time until metastases develop. With the advent of these second-generation AR-targeted agents, we will be using them sooner, for sure. What does that mean later on? So, if a patient’s cancer progresses on these agents, then he’s more likely to get chemotherapy and other drugs when the cancer becomes metastatic.

Charles J. Ryan, MD: Nonmetastatic castration-resistant prostate cancer is an interesting entity, because there are a couple of things that could happen. One is it could go away, because with novel imaging agents we might be able to detect metastases. And so, it could be that some of the patients who–5 years ago and even today–we think of as having nonmetastatic disease actually have metastatic disease, but we’re just not detecting it because we’re not using the most sophisticated imaging modality.

Over the course of the next few years, we’re going to see data on PSMA (prostate-specific membrane antigen)-PET scans and other types of new-generation imaging modalities that might tell us some of the patients who have nonmetastatic disease actually have metastatic disease. That’s number one. Number 2 is that the future for those patients who have slowly progressive nonmetastatic disease is that we will be able to preserve them into that nonmetastatic state with next-generation androgen receptor antagonists, most likely. It’s also possible that we’ll look at immunotherapies in this setting, but I really think that the future in the short run is with integrating newer AR-targeted agents into this group of patients.

The landscape for nonmetastatic castration-resistant prostate cancer is changing because we’ll likely have therapies in that space whereas previously, we really haven’t had anything. This has been an area that I actually think is about 25% of our castration-resistant patient population, at least it is in some estimates. This is an area where physicians like myself have been treating patients with off-label therapies. We haven’t had an on-label therapy in this group of patients. We’ve simply been observing them, waiting for them to develop metastatic disease. It has always felt a little unsatisfactory that we should have to wait for a complication or progression to occur before we intervene, when we know that therapies may be beneficial. So, I’m quite excited about the possibility of having a therapy that’s available for nonmetastatic disease because I can confidently tell patients that I’m going to have a significant chance to prevent metastasis from occurring.

Transcript Edited for Clarity 
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