Selected Podcast
Pluvicto for Metastatic Castrate Resistant Prostate Cancer
Robert Zlotecki M.D., PhD describes the factors that make a patient a candidate for Pluvicto treatment for prostate cancer. He explains the process of treatment through a series of Pluvicto infusions for prostate cancer and he outlines the current shift in thinking regarding systemic radiopharmaceutical therapy for prostate cancer.
Featuring:
Robert Zlotecki, M.D., PhD
During my 15 years at the University of Florida, one of my areas if focus has been the multidisciplinary management of patients with pediatric sarcomas of soft tissue and bone. Currently, I serve as the Medical Director for the UF Department of Radiation Oncology and participate in several national professional societies and committees, including the American Board of Radiology and the Radiologic Society of North America. Clinical research productivity includes 55 peer-reviewed publications and several supporting grants. My clinical practice integrates translational research collaborations with our UF Prostate Disease Center, and also with our medical physics and informatics programs. Direct collaboration with colleagues in the UF Cancer and Genetics Institute connects my Ph.D. training in Pharmacology with the applied radiation biology, to facilitate the translation of laboratory research to clinical application in the delivery of multi-modality integrated cancer therapies. My specific technical interests include the management of metastatic cancers utilizing the technologies of Stereotactic Body Radiotherapy (SBRT) with Image Guidance (IGRT), which employ accelerated hypo-fractionation dose delivery protocols; and the development of emerging mobile and interactive technologies to enable an eMedical infrastructure to facilitate the collection of physician and patient reported quality and satisfaction data related to cancer diagnosis, treatment, and Quality of Life (QoL) outcomes.
Transcription:
The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie Cole (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And joining me is Dr. Robert Zlotecki. He's the medical director and a professor in the Department of Radiation Oncology at the University of Florida College of Medicine. And he practices at UF Health Shands Hospital. He's here to highlight Pluvicto for PSMA, positive metastatic castrate-resistant prostate cancer.
Dr. Zlotecki, welcome back. And thank you so much for being with us today. As we get into this absolutely fascinating topic, can you tell us a little bit first about metastatic castrate-resistant prostate cancer? Define it for us. Describe what you've been seeing in the trends, and you can even give us a little bit of diagnostic criteria to be labeled as hormone-refractory.
Dr Robert Zlotecki: So as everybody understands that prostate cancer is now one of the biggest killers of older men; lung cancer, no longer and heart disease, not so much even there. But prostate cancer, one of the biggest cancer risks and, although prostate cancer in many respects is now very well early diagnosed and managed and can be cured. There's unfortunately a segment of men who do have very high risk aggressive prostate cancer that does not respond to therapies well at all, becomes let's say rogue in some respects and becomes independent of the classic method of control, which is applicable to also to women with breast cancer, through the pathways of hormone manipulation.
These patients unfortunately develop metastatic disease early. It becomes aggressive and the use of hormone therapies only will work for so long in controlling or containing this disease. When the prostate cancer becomes independent of the hormone pathways, regulatory pathways, the metastatic spread can become aggressive and we need other pathways of treatment, the classic path, and then becomes the use of systemic chemotherapy agents in the Taxol or taxane family. But now, we're looking at a different method by targeting the prostate-specific membrane antigen, a marker on the cell system of cancer cells that would be amenable to directly bound or avid targeting and delivery with a radioactive element.
Melanie Cole (Host): Well, thank you for that, Dr. Zlotecki. And for other providers that are relatively new to these exciting advances, can you outline the current shift in thinking regarding systemic radiopharmaceutical therapies for prostate cancer as the treatment options in the past you've described for us? What's changed now? You can speak about Pluvicto, because the FDA has approved this now. So speak a little bit about this current shift in thinking.
Dr Robert Zlotecki: So Pluvicto has been FDA approved based on very recent clinical trials that have looked at the population of gentlemen with some of the most aggressive prostate cancer and who have progressed after the taxane chemotherapies have failed them. These gentlemen were demonstrated to have a significant advantage in their survival, their well-being and quality of lives with the use of Pluvicto or lutetium 177 PSMA radiotherapy treatment, systemically delivered. And this agent is now also in clinical trials for patients with earlier presentations of the prostate cancer. For example, patients who have not seen any taxane-based chemotherapy, because many gentlemen just do not want to accept taking a standard systemic chemotherapy drug, regardless of the tolerance of it, which taxane have variable effects in some folks, particularly neuropathy issues. There's also a clinical trial in gentlemen who are still hormone-sensitive and have not become castrate-resistant. So there's a steady shift of this type of therapy, what's called radioligand, very specific target therapy forward in the disease of prostate cancer.
Melanie Cole (Host): So what are some of the factors? You mentioned a few. I'd like you to expand a little that make a patient a candidate for this type of treatment. Now, is it used standalone at the point when a hormone no longer works? If they're on XTANDI or one of those? Is it used adjuvant? Tell us a little bit about patient selection?
Dr Robert Zlotecki: Right now, the FDA indications criteria for the prescription and delivery of Pluvicto include gentlemen who are with metastatic castrate-resistant prostate cancer who have progressed, whether they've received XTANDI or abiraterone, or other agents in addition to standard conventional androgen deprivation therapy. But the key issue is these gentlemen must also have had a trial of a taxane-based chemotherapy regimen and progressed on that drug therapy.
The other thing that must be demonstrated and confirmed is that the patient has a positive PSMA PET scan, which demonstrates uptake or avidity of the PSMA ligand and basically binding effectively to the prostate cancer cells. Once those criteria are met and the patient does have an acceptable performance status as well as acceptable laboratory parameters of both bone marrow and kidney function and also liver function, then the patient would be a very good candidate for systemic therapy with the drug Pluvicto, which has a huge advantage over previous systemic radiotherapy treatments and that it not only effectively targets and treats metastatic disease in the bone, but it will target cancer cells that are in lymph nodes and other soft tissues or organs, which previous agents could not reach.
Melanie Cole (Host): Wow. That is so exciting. What an exciting time to be in your field, doctor. So what have the clinical trials shown as far as its effectiveness and where do you see this headed in the future?
Dr Robert Zlotecki: The very good thing is that it has shown an absolute survival advantage in the patients who have been treated with this agent and who have unfortunately become resistant to practically all other therapeutic lines. That is a huge absolute there. Where do we see this type of therapy going? Just as the currently active clinical trials in progress are directing us, we are expecting this to come forward in the regimen of cancer therapeutics in prostate cancer, such that it'll be applied more effectively in the cure of, well, prostate cancer maybe, but in the control of metastatic prostate cancer or aggressive and resistant cancers, and may be replacing some therapies that only have minimal efficacy or limited time of efficacy, such as the taxane-based chemotherapy or some pathways of advanced or unique hormonal suppression. So, again, it won't be used in combination, but it will be coming forward in the overall regimen of systemic treatment for high risk and metastatic prostate cancers.
This is something we would also expect to see in other lines of cancer treatment development. Similar pathways of treatment have been evoked in metastatic neuroendocrine pancreatic cancer. And we should see it come along in other highly aggressive and metastatic cancers.
Melanie Cole (Host): As we wrap up, doctor, what a great guest you are. Can you please tell other providers when you feel it's important to refer and if there's any clinical trials or studies that you would like them to know about or to get their patients involved in? Please tell us about those now.
Dr Robert Zlotecki: Right now, there are several clinical trials. Most notably sponsored both by the Novartis, Corporation, which is PSMA4 for patients who have not been treated with taxane-based chemotherapy yet. The radiation therapy oncology group in cooperation with other clinical trial organizations has advanced patients with hormone-sensitive prostate cancer into treatment with the PSMA lutetium agents, Pluvicto. The biggest effect that we're hoping for to see in these trials, again, as an endpoint is an absolute improvement in overall survival for these patients. But we're also expecting, significant delays in any progression of the disease and, again, an overall improvement in the patient's quality of life by not only effectively managing their disease, but also by not subjecting them to side effects, greater effects from drugs and other therapies that may not have the efficacy and the viability that this agent hopefully should demonstrate.
Melanie Cole (Host): Thank you so much, Dr. Zlotecki, for joining us today. To refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. For more updates on the latest medical advancements, breakthroughs and research, you can always follow us on your social channels. I'm Melanie Cole.
The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie Cole (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And joining me is Dr. Robert Zlotecki. He's the medical director and a professor in the Department of Radiation Oncology at the University of Florida College of Medicine. And he practices at UF Health Shands Hospital. He's here to highlight Pluvicto for PSMA, positive metastatic castrate-resistant prostate cancer.
Dr. Zlotecki, welcome back. And thank you so much for being with us today. As we get into this absolutely fascinating topic, can you tell us a little bit first about metastatic castrate-resistant prostate cancer? Define it for us. Describe what you've been seeing in the trends, and you can even give us a little bit of diagnostic criteria to be labeled as hormone-refractory.
Dr Robert Zlotecki: So as everybody understands that prostate cancer is now one of the biggest killers of older men; lung cancer, no longer and heart disease, not so much even there. But prostate cancer, one of the biggest cancer risks and, although prostate cancer in many respects is now very well early diagnosed and managed and can be cured. There's unfortunately a segment of men who do have very high risk aggressive prostate cancer that does not respond to therapies well at all, becomes let's say rogue in some respects and becomes independent of the classic method of control, which is applicable to also to women with breast cancer, through the pathways of hormone manipulation.
These patients unfortunately develop metastatic disease early. It becomes aggressive and the use of hormone therapies only will work for so long in controlling or containing this disease. When the prostate cancer becomes independent of the hormone pathways, regulatory pathways, the metastatic spread can become aggressive and we need other pathways of treatment, the classic path, and then becomes the use of systemic chemotherapy agents in the Taxol or taxane family. But now, we're looking at a different method by targeting the prostate-specific membrane antigen, a marker on the cell system of cancer cells that would be amenable to directly bound or avid targeting and delivery with a radioactive element.
Melanie Cole (Host): Well, thank you for that, Dr. Zlotecki. And for other providers that are relatively new to these exciting advances, can you outline the current shift in thinking regarding systemic radiopharmaceutical therapies for prostate cancer as the treatment options in the past you've described for us? What's changed now? You can speak about Pluvicto, because the FDA has approved this now. So speak a little bit about this current shift in thinking.
Dr Robert Zlotecki: So Pluvicto has been FDA approved based on very recent clinical trials that have looked at the population of gentlemen with some of the most aggressive prostate cancer and who have progressed after the taxane chemotherapies have failed them. These gentlemen were demonstrated to have a significant advantage in their survival, their well-being and quality of lives with the use of Pluvicto or lutetium 177 PSMA radiotherapy treatment, systemically delivered. And this agent is now also in clinical trials for patients with earlier presentations of the prostate cancer. For example, patients who have not seen any taxane-based chemotherapy, because many gentlemen just do not want to accept taking a standard systemic chemotherapy drug, regardless of the tolerance of it, which taxane have variable effects in some folks, particularly neuropathy issues. There's also a clinical trial in gentlemen who are still hormone-sensitive and have not become castrate-resistant. So there's a steady shift of this type of therapy, what's called radioligand, very specific target therapy forward in the disease of prostate cancer.
Melanie Cole (Host): So what are some of the factors? You mentioned a few. I'd like you to expand a little that make a patient a candidate for this type of treatment. Now, is it used standalone at the point when a hormone no longer works? If they're on XTANDI or one of those? Is it used adjuvant? Tell us a little bit about patient selection?
Dr Robert Zlotecki: Right now, the FDA indications criteria for the prescription and delivery of Pluvicto include gentlemen who are with metastatic castrate-resistant prostate cancer who have progressed, whether they've received XTANDI or abiraterone, or other agents in addition to standard conventional androgen deprivation therapy. But the key issue is these gentlemen must also have had a trial of a taxane-based chemotherapy regimen and progressed on that drug therapy.
The other thing that must be demonstrated and confirmed is that the patient has a positive PSMA PET scan, which demonstrates uptake or avidity of the PSMA ligand and basically binding effectively to the prostate cancer cells. Once those criteria are met and the patient does have an acceptable performance status as well as acceptable laboratory parameters of both bone marrow and kidney function and also liver function, then the patient would be a very good candidate for systemic therapy with the drug Pluvicto, which has a huge advantage over previous systemic radiotherapy treatments and that it not only effectively targets and treats metastatic disease in the bone, but it will target cancer cells that are in lymph nodes and other soft tissues or organs, which previous agents could not reach.
Melanie Cole (Host): Wow. That is so exciting. What an exciting time to be in your field, doctor. So what have the clinical trials shown as far as its effectiveness and where do you see this headed in the future?
Dr Robert Zlotecki: The very good thing is that it has shown an absolute survival advantage in the patients who have been treated with this agent and who have unfortunately become resistant to practically all other therapeutic lines. That is a huge absolute there. Where do we see this type of therapy going? Just as the currently active clinical trials in progress are directing us, we are expecting this to come forward in the regimen of cancer therapeutics in prostate cancer, such that it'll be applied more effectively in the cure of, well, prostate cancer maybe, but in the control of metastatic prostate cancer or aggressive and resistant cancers, and may be replacing some therapies that only have minimal efficacy or limited time of efficacy, such as the taxane-based chemotherapy or some pathways of advanced or unique hormonal suppression. So, again, it won't be used in combination, but it will be coming forward in the overall regimen of systemic treatment for high risk and metastatic prostate cancers.
This is something we would also expect to see in other lines of cancer treatment development. Similar pathways of treatment have been evoked in metastatic neuroendocrine pancreatic cancer. And we should see it come along in other highly aggressive and metastatic cancers.
Melanie Cole (Host): As we wrap up, doctor, what a great guest you are. Can you please tell other providers when you feel it's important to refer and if there's any clinical trials or studies that you would like them to know about or to get their patients involved in? Please tell us about those now.
Dr Robert Zlotecki: Right now, there are several clinical trials. Most notably sponsored both by the Novartis, Corporation, which is PSMA4 for patients who have not been treated with taxane-based chemotherapy yet. The radiation therapy oncology group in cooperation with other clinical trial organizations has advanced patients with hormone-sensitive prostate cancer into treatment with the PSMA lutetium agents, Pluvicto. The biggest effect that we're hoping for to see in these trials, again, as an endpoint is an absolute improvement in overall survival for these patients. But we're also expecting, significant delays in any progression of the disease and, again, an overall improvement in the patient's quality of life by not only effectively managing their disease, but also by not subjecting them to side effects, greater effects from drugs and other therapies that may not have the efficacy and the viability that this agent hopefully should demonstrate.
Melanie Cole (Host): Thank you so much, Dr. Zlotecki, for joining us today. To refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. For more updates on the latest medical advancements, breakthroughs and research, you can always follow us on your social channels. I'm Melanie Cole.