“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer”

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] Jonathan Starr and Brad Power June 19, 2023 Meeting Summary Prostate cancer is not curable for most patients once it becomes metastatic. Advanced prostate cancer patients find themselves trying treatments that work for a while until they fail, then moving on to another therapy.

They are continuously worrying about the effects of their cancer and treatments on their quality of life, especially bone metastases and the side effects of hormone deprivation therapy, which leads to bone density issues and muscle loss, among others.

Prostate cancer, like all cancers, is unique to each patient, with some patients receiving molecularly targeted therapy, and some patients responding to immunotherapy. New drugs, such as those which use a radiopharmaceutical are now coming to market. Patients might also consider experimental combination therapies, for example combining a radiopharmaceutical with a PARP inhibitor or immunotherapy.

Alpha and beta particles can also be combined experimentally, as well as alpha or beta particles with radiation sensitizers, modulating the way the drugs alter DNA. The importance of lifestyle and prevention of complications in advanced prostate cancer is another concern. A.

Oliver Sartor, MD, recently moved to Mayo Clinic, is uniquely qualified to review this complicated landscape and discuss research on immunotherapies, radiopharmaceuticals, and combinations in prostate cancer.

His research has mainly focused on translational science and clinical research trials of advanced prostate cancer since 1990, and he is recognized as an expert in that field through his contributions to the practice and the publishing of over 500 peer- reviewed articles and numerous book chapters and reviews.

He has been PI or co-PI on pivotal trails that have helped to change the landscape of advanced disease including radium-223, cabazitaxel, and Pluvicto (PSMA-617 Lu-177). Bullets from Russ Hollyer: · PSMA targeted alpha therapy delivers highly potent, selective, and local alpha radiation to cancer cells and the tumor microenvironment. The side effects are being worked on.

· BAT provides an interesting way to control PCa. Dr. Sartor has used it approximately 90 times. · It might not be necessary to swing testosterone high and then low. Constant high testosterone is an intriguing possibility. · Prior therapies, future order, patient preference, and side effects should be considered prior to choosing a therapy.

· Darolutamide should be preferrable to Xtandi based on side effects. From Ben Nathanson: He was frank about how slim the survival benefits have been in trials and how few men can currently benefit from precision medicine, issues that we as patients are painfully aware of but many doctors seem to evade.

“The Current and Fut

son: He was frank about how slim the survival benefits have been in trials and how few men can currently benefit from precision medicine, issues that we as patients are painfully aware of but many doctors seem to evade. I appreciated the mindshare he's giving to inadequately

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] understood areas like chromosomal disorder and noncoding DNA. Even his quick description of when PARPi shows benefit, including cases like DNA methylation that don't show up in genomic studies, was invaluable. From Arthur Bruno: 1.I was surprised by his suggestion of continuous Hi T. 2.

I noted that his strongest endorsement for the next major advancement in PCa care was the alpha particle radioligand therapy. Makes sense to me. From Jeff Dwyer: Sartor presented as such an open and giving man and he impressed me with his candor.

He was quick to point out the reality of the Pharma industry control on the development of new drug protocols along with the expense of RCTs and explained that he doesn’t spend a lot of his thinking time on treatment programs for his patients that will not be reimbursed by insurers. I had considered a trip to Tulane - dipping into NO can usually be a lot of fun - to consult personally with him.

But, the pandemic nicked that. He offered his email address and appears open to remote consultations. If this turns out to be possible, we’d all be very fortunate.

The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] Meeting Notes The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Discussion Outline 1.Introduction to Dr. Oliver Sartor. 2.Prevention and treatment of adenocarcinoma. (5:34) 3.Tissue biopsy vs. circulating tumor DNA tests. (10:44) 4.

What is the status of the sabizabulin treatment for prostate cancer? (18:45) 5.The RGCC Greek test. (28:52) 6.High T vs. BAT (34:11) 7.

roduction to Dr. Oliver Sartor. 2.Prevention and treatment of adenocarcinoma. (5:34) 3.Tissue biopsy vs. circulating tumor DNA tests. (10:44) 4.What is the status of the sabizabulin treatment for prostate cancer? (18:45) 5.The RGCC Greek test. (28:52) 6.High T vs. BAT (34:11) 7.How do you look at PSA and disease-specific survival? (39:57) 8.How does proteomics fit into precision medicine?

(45:58) 9.What are your questions about prostate cancer? (51:19) 10.Novartis and the Lutetium trial. (59:18) 11.The durability of testosterone. (1:05:11) 12.Next steps for patients with high-risk prostate cancer. (1:13:07) 13.How do you know when to start treatment? (1:17:19) 14.Radium vs. Taxane for treatment of prostate cancer. (1:21:55) 15.A quick table of RNA expression in prostate cancer.

(1:29:25) 16.High mutational burden and mismatch repair deficiencies. (1:34:40) 17.Pelvic lymph nodes and genomics. (1:40:19) 18.Dr. Sartor’s recommendation for patients with mismatch repair deficient and genomic. (1:47:57) 19.What is the tolerability of a PARP inhibitor? (1:52:54) 20.PSMA PET vs. Choline scans.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] We're very honored to have Dr. Oliver Sartor with us today. Dr. Sartor, you'll remember that part of our connection is through Jeff Hoffman, who was a classmate of yours at Tulane back in medical school, and Jeff is my cousin. Jeff pointed me to Dr. Sartor, and Dr.

Sartor has been very helpful in providing advice to a number of the patients we've had, especially, Bryce Olson, on some of the choices that he faced. A number of patients in our community have requested to have a conversation with Dr. Sartor. He's moving from Tulane to Mayo Clinic. Does that mean a physical move for you? Oliver Sartor 2:03 Yes.

I realize as I pull up the slides, that it shows me still at Tulane. I'm at Mayo now. I'm happy to give you my email and stuff like that. Let me let me put that in the chat. But yes, I'm physically at Mayo. Brad Power 2:21 So you're beaming to us now from Minnesota? Oliver Sartor 2:24 Beaming to you from Minnesota. I'm in Rochester, Minnesota, right at this particular moment.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] Brad Power 2:30 Dr. Sartori is going to run through a few slides really quickly, five or 10 minutes, and then we will mostly have Q&A. We had some email conversations about questions that pat

ochester, Minnesota, right at this particular moment.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] Brad Power 2:30 Dr. Sartori is going to run through a few slides really quickly, five or 10 minutes, and then we will mostly have Q&A. We had some email conversations about questions that patients had in advance.

There's a request that you focus on castrate resistant prostate cancer patients who are beyond hormone sensitive prostate cancer so that we get kind of skinnier branches of people that are more advanced, as much as you can. Oliver Sartor 3:09 I’m at Mayo Clinic right now. I’ve been involved with advanced prostate cancer for a long time.

And I think first of all, you have to have some feeling for where the field is before you can understand the rest.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] This particular slide encapsulates all the phase three trials that have been shown to have an overall survival advantage. All of these are in the New England Journal, except for one. That's the TROPIC trial. And we have a variety of things that I think are sort of noteworthy.

So first, I'll make a comment that when you look at the overall survival benefit, I think the first thing that you would conclude as a patient is that this is pretty unimpressive. And I think it is not as impressive as we would like. But that's just the reality.

And there are a variety of reasons for this, some there may be crossover and but nevertheless, these are factual data that I think is important for people to know. A couple of other things. The field has really been changing since the early trials showed a benefit for things like Sipuleucel-T, that's Provenge. I don't know how relevant it is today. The same is probably true for radium.

Sipuleucel-T was FDA approved in 2010, radium FDA approved in 2013. And there's really been a wholesale change since then, if we want to look at clinical decision making, and I can spend an hour on this, but I won't. You have to kind of think about, first of all, what is available and what is affordable. And that's not always so clear, a lot of these things are very expensive now.

So that's really a problem.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] There are a lot of therapies that may not be suitable for everybody, you know, performance status, age, comorbidities, laboratory assessment symptoms all sort of dictate how we think prior therapies, response and resistance and duration of prior therapies. I just spoke to a patient today.

He underwent chemotherapy with no response. I’m probably not going to give him another chemotherapy. Oh, it's an intolerance of prior therapies burden of disease, I'll go mass not only go BAT. Where's the disease located?

he Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] Brad Power 2:30 Dr. Sartori is going to run through a few slides really quickly, five or 10 minutes, and then we will mostly have Q&A. We had some email conversations about questions that patients had in advance.

There's a request that you focus on castrate resistant prostate cancer patients who are beyond hormone sensitive prostate cancer so that we get kind of skinnier branches of people that are more advanced, as much as you can. Oliver Sartor 3:09 I’m at Mayo Clinic right now. I’ve been involved with advanced prostate cancer for a long time.

And I think first of all, you have to have some feeling for where the field is before you can understand the rest.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] This particular slide encapsulates all the phase three trials that have been shown to have an overall survival advantage. All of these are in the New England Journal, except for one. That's the TROPIC trial. And we have a variety of things that I think are sort of noteworthy.

So first, I'll make a comment that when you look at the overall survival benefit, I think the first thing that you would conclude as a patient is that this is pretty unimpressive. And I think it is not as impressive as we would like. But that's just the reality.

And there are a variety of reasons for this, some there may be crossover and but nevertheless, these are factual data that I think is important for people to know. A couple of other things. The field has really been changing since the early trials showed a benefit for things like Sipuleucel-T, that's Provenge. I don't know how relevant it is today. The same is probably true for radium.

Sipuleucel-T was FDA approved in 2010, radium FDA approved in 2013. And there's really been a wholesale change since then, if we want to look at clinical decision making, and I can spend an hour on this, but I won't. You have to kind of think about, first of all, what is available and what is affordable. And that's not always so clear, a lot of these things are very expensive now.

So that's really a problem.

“The Current and Future Landscape of Metastatic Castrate Resistant Prostate Cancer” (Oliver Sartor) [#62] There are a lot of therapies that may not be suitable for everybody, you know, performance status, age, comorbidities, laboratory assessment symptoms all sort of dictate how we think prior therapies, response and resistance and duration of prior therapies. I just spoke to a patient today.

He underwent chemotherapy with no response. I’m probably not going to give him another chemotherapy. Oh, it's an intolerance of prior therapies burden of disease, I'll go mass not only go BAT. Where's the disease located? Bone only, liver, pelvic lymph nodes only – makes a big difference, particularly liver.