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Sequencing and Layering of Drugs in CRPC

Panelists: Raoul S. Concepcion, MD, Comprehensive Prostate Center in Nashville; Evan Y. Yu, MD, Fred Hutchinson Cancer Research Center; Michael A. Carducci, MD, FACP, Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins Hospital; Neal D. Shore, MD, FACS, Carolina Urologic Research Center; Glen Gejerman, MD, DABR, John Theurer Cancer Center
Published: Tuesday, Jul 25, 2017



Transcript:

Raoul S. Concepcion, MD, FACS:
Again, as we talk about the journey, especially for these particular patients who, unfortunately, will develop metastatic castration-resistant prostate cancer, the problem is that all of the trials for all of these agents—which, again, are different mechanistically—were all single-agent trials, but they did show a survival benefit.

So, again, one of the biggest things that all of our colleagues and our peers are asking is, “What about combination therapy? What about sequencing? What about layering?” Neal, you, Evan, and I are all involved on a working panel called the RADAR Working Group. Do you want to talk about the RADAR II recommendations?

Neal D. Shore, MD, FACS: The RADAR II paper was just recently approved for publication. It followed RADAR I, which was previously published in Urology. RADAR II is an attempt to get a consensus from key opinion leaders in medical oncology, urology, radiation oncology, and pathology, to get together and say, “We had this embarrassment of riches, as it’s been described, of 5 or 6 new therapies that received registration approval—all done, typically, with their comparator being a control or maybe a steroid. But what do we do now?” What do we do now that we have a half-dozen agents and we have a patient who has various nuanced parameters: bone, soft tissue, visceral, other comorbidities, etc? What do we do when they start to see PSA (prostate-specific antigen) progression? What do we do when they are no longer clinically benefiting from the Prostate Cancer Working Group 3 descriptor?

Rather than waiting for the evidence-based data, oftentimes the level 1 data that take years, what do you do when you’re sitting knee-to-knee in the clinic? For anybody who is watching, and they have that patient in their clinic, what do you tell them now? Are you maximizing their therapy? What sort of advice could we give? So, that was the notion of RADAR II; that’s just a definition. We talk about sequencing, which is monolithic—one drug after another, after another, which is typically not what’s done in most of medical oncology for solid tumor metastatic disease. Yet, we do that in prostate cancer because we haven’t had the information. We sequence and then folks ask, “Can I?” or “Do I combine?” or “Is it safe?” And then, there is the notion of layering.

Layering is, “I’ve been on something. I’m not going to start another drug, concomitantly, at exactly the same time, but I’m going to add it on afterwards.” That’s layering—getting to a second or third therapy without removing the first or the second therapy. That was the notion of layering. I would strongly recommend that folks who are devotees to treating CRPC patients read the paper, because there was a lot of consensus behind the recommendations.

Raoul S. Concepcion, MD, FACS: We’re not going to really go into all the new therapies. We’ve already been there. We know that we’ve got all these therapies—we’ve got taxanes, androgen synthesis inhibitors, androgen receptor blockade, alpha-emitting radiopharmaceuticals, and immunotherapy. And we all know that, again, disease will develop resistance and they will ultimately fail. Right now, the real problem is that we don’t have any predictive markers to tell us when that patient is failing.

Transcript Edited for Clarity

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Transcript:

Raoul S. Concepcion, MD, FACS:
Again, as we talk about the journey, especially for these particular patients who, unfortunately, will develop metastatic castration-resistant prostate cancer, the problem is that all of the trials for all of these agents—which, again, are different mechanistically—were all single-agent trials, but they did show a survival benefit.

So, again, one of the biggest things that all of our colleagues and our peers are asking is, “What about combination therapy? What about sequencing? What about layering?” Neal, you, Evan, and I are all involved on a working panel called the RADAR Working Group. Do you want to talk about the RADAR II recommendations?

Neal D. Shore, MD, FACS: The RADAR II paper was just recently approved for publication. It followed RADAR I, which was previously published in Urology. RADAR II is an attempt to get a consensus from key opinion leaders in medical oncology, urology, radiation oncology, and pathology, to get together and say, “We had this embarrassment of riches, as it’s been described, of 5 or 6 new therapies that received registration approval—all done, typically, with their comparator being a control or maybe a steroid. But what do we do now?” What do we do now that we have a half-dozen agents and we have a patient who has various nuanced parameters: bone, soft tissue, visceral, other comorbidities, etc? What do we do when they start to see PSA (prostate-specific antigen) progression? What do we do when they are no longer clinically benefiting from the Prostate Cancer Working Group 3 descriptor?

Rather than waiting for the evidence-based data, oftentimes the level 1 data that take years, what do you do when you’re sitting knee-to-knee in the clinic? For anybody who is watching, and they have that patient in their clinic, what do you tell them now? Are you maximizing their therapy? What sort of advice could we give? So, that was the notion of RADAR II; that’s just a definition. We talk about sequencing, which is monolithic—one drug after another, after another, which is typically not what’s done in most of medical oncology for solid tumor metastatic disease. Yet, we do that in prostate cancer because we haven’t had the information. We sequence and then folks ask, “Can I?” or “Do I combine?” or “Is it safe?” And then, there is the notion of layering.

Layering is, “I’ve been on something. I’m not going to start another drug, concomitantly, at exactly the same time, but I’m going to add it on afterwards.” That’s layering—getting to a second or third therapy without removing the first or the second therapy. That was the notion of layering. I would strongly recommend that folks who are devotees to treating CRPC patients read the paper, because there was a lot of consensus behind the recommendations.

Raoul S. Concepcion, MD, FACS: We’re not going to really go into all the new therapies. We’ve already been there. We know that we’ve got all these therapies—we’ve got taxanes, androgen synthesis inhibitors, androgen receptor blockade, alpha-emitting radiopharmaceuticals, and immunotherapy. And we all know that, again, disease will develop resistance and they will ultimately fail. Right now, the real problem is that we don’t have any predictive markers to tell us when that patient is failing.

Transcript Edited for Clarity
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