Advanced Prostate Cancer: Testing & Treatment Options Review

•Liquid biopsy, e.g., the Tempus xF+ test, can provide biomarkers for targeted treatments.

•Proteomic analysis, e.g., mProbe tissue analysis, can provide new biomarkers for targeted treatments.

•Standard Uptake Values from a PSMA PET scan will indicate whether he is likely to have a response to PSMA-targeted radiation therapy.

•Current status of PDL1/PD1, tumor mutation burden, and MSS/MSI, can help predict whether he will likely be responsive to immunotherapy.

•Whole genome and RNA sequencing can identify biomarkers which may be targetable.

•Bone biopsy, possibly the bone aspirate liquid biopsy being researched by Peter Kuhn, to be able to analyze bone tumors. What additional treatment options were suggested?

•An Androgen Receptor (AR) degrader (ARV or ARV-766 clinical trial), given the high expression of AR as noted in the Caris report.

•CAR-T, if there are indications that an immunotherapy might work.

•Drug combinations of abiraterone + olaparib + sulindac, carboplatin + degarelix + sulindac, apalutamide + lutetium lu 177 vipivotide tetraxetan + sulindac, abiraterone + olaparib, carboplatin + degarelix, and apalutamide + lutetium lu 177 vipivotide tetraxetan 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 Cancer Patient Lab/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. 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 Cancer Patient Lab/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. SUMMARY KEYWORDS psa, treatment, tissue, started, report, liquid biopsy, clinical trial, adt, robert, chemo, biopsy, test, cancer, respond, little bit, therapy, psm, scan, chemotherapy, metastases SPEAKERS Robert Ellis (62%), Brian McCloskey (10%), Rick Stanton (9%), Amit Gattani (6%), Brad Power (6%), Ally Perlina (4%), Mike Yancey (3%) Brad Power Today is the type of Prostate Cancer Lab meeting where we have one of the patients in our community review his case. Today we are going to hear from Robert Ellis. Please note that the Information and opinions shared on this website or platform or during discussions and presentations are not intended as medical advice. It is important to consult with a healthcare professional about your specific situation before making any decisions related to your health. Also, everything that you say can and will be made public. Anyone who speaks, I always send out the transcript for an opportunity to review and revise. We will not publish anything unless anyone who says something approves it. Those are our standards. We have to make sure that everyone is protected from anything that they might say. Robert is going to review his case and look for some feedback on ideas to help him with his testing and treatment decisions. Robert Ellis (1:27) I want to thank everybody for this opportunity to get your input and review my case. I apologize in advance that I don't have as much information as I'd hoped to have. I was scheduled to have a PSMA scan, and I had a biopsy in October that did not reveal any usable tissue. My primary aims for this call are: I would love some guidance on specifically what kind of testing options I should talk to my doctor about to be able to identify some markers that might be targetable for treatment. And the second thing is: right now in my conversations with my oncologist, I really have two treatment options in the wings. I'd like to know if there are some other treatment options that are aligned with my sort of treatment principles which I'll share. And possibly combination treatments and things like that. In other words, what other things should I be talking to my doctor about or see if I can get lined up for after the current treatment that I'm on, after I stop responding to my current treatment. A little bit of a disclaimer: last night I saw Rick's email and looked at his depiction of his cancer history and was a little intimidated. And then I thought, I better go through all my notes on the Google Drive. And I found Brian's files, and that was pretty intimidating too. I'm going to show you an unfinished symphony. I'm inspired by the work that Rick and Brian have done, and I'm going to be more diligent about maintaining my records going forward. Rick Stanton (3:40) Don't forget Eric. He did a really cool depiction as well. Robert Ellis (4:09) Here is my spreadsheet with a complete record of my PSA. I have not added a legend like in Rick's beautiful charts. This chart here was provided by xCures. It's a little out of date. They put this together for me back in 2021. The reason I haven't had an updated one is I keep waiting to get new test results, but then I haven't gotten any. I was diagnosed on October 23, 2017. When I had my first PSA, it was 22.3. The initial spike is because it took me a while before I began treatment. Shortly after that I went on a clinical trial. I started on ADT, which on the xCures chart was casodex followed by Lupron. Then abiraterone was added. I was on a clinical trial at UCSF, which was a combination of five treatments of focal radiation to the prostate, and 13 rounds of pembrolizumab every three weeks. I responded well. It was difficult to say whether that was the ADT or the clinical trial, but I responded pretty well. By May of 2019, my PSA was fractional at 0.384. When I was at the end of this clinical trial, they stopped everything. I had no treatment at all. I felt really good for about three or four months, but at around five months I started to have pain again. I have metastases to my tissue of tuberosities (a large prominence on a bone usually serving for the attachment of muscles or ligaments). When I had the next PSA, I was at 28.73. So they started me on ADT again, Lupron and abiraterone, and then responded to that. At the beginning of 2021 I started to become castrate resistant. I was on the same treatment but my PSA was rising. The next drop is where I started dutasteride, which is known to give a false PSA drop. It showed my PSA dropped when I began dutasteride, but it was not. It wasn't really treating the cancer. It was a false reading, and it spiked again after that. I began chemotherapy in October of 2021. The chemotherapy was a combination of carboplatin, because I have BRCA2, and docetaxel, initially, at a total of 16 rounds. Three of those were carboplatin and cabazitaxel. I asked to try cabazitaxel to see if the side effects were any less onerous than the docetaxel. They were worse: more neuropathy in my feet, which I still have. But I responded pretty well to chemotherapy for some time. When my PSA started to go up again, we stopped the chemotherapy, and I began Rubraca (rucaparib, a PARP inhibitor). That was partly because earlier xCures had recommended a clinical trial that was a combination of olaparib and radium 233. Olaparib had always been in the wings, but I was advised not to do a PARP inhibitor earlier because there was a new generation in the works, and Rubraca was one of those. By the time the chemotherapy began to fail, I started the Rubraca. Just after I started the Rubraca I managed to get my oncologist Dr. Koontz to speak with Dr. McKay about bipolar androgen therapy. It took a while for them to connect. In that interim, we started the Rubraca so that I would be on some treatment. I'm responding to it. So we'll continue until I stop responding. Dr. Koontz was open to considering bipolar androgen therapy. After that, though, I learned that there are some risks involved and the responses are mixed. I have had CT scans during 2018 and 2019 Those were all stable. I was supposed to have a PSMA scan last fall, but for some reason they ran the wrong test. They did a PET CT instead of PSMA. I was supposed to have a PSMA this week on Monday, but the weather prevented that. So I'm having that on the 26th. Brad Power (10:37) In early 2022 you were on a PARP inhibitor. You were probably still on Lupron. What was the combination you were on? We often talked about drug combinations, but you were on a list of chemo and a PARP inhibitor and maybe ADT? Robert Ellis (10:58) I was not on the PARP inhibitor Rubraca. I started that after the chemo failed. All of this time I was on – I can't remember exactly when I started – Orgovyx (relugolix). I started using Orgovyx instead of Lupron. I stopped the abiraterone when I became castrate resistant. This year is when I started the chemo. In October of 2021 I was still on Orgovyx. This was all chemo and Orgovyx. There was a little bump. By the way, I have no way of knowing, but during this time I was also experimenting with taking various supplements that were potential chemo sensitizers. I have no idea if they made any difference because I started to have a little rise in my PSA here. And then I got a little more mileage out of it. But then I just started failing – my PSA was rising. So I stopped the chemo. I'm still on Orgovyx. I started Rubraca in November and October. By the way, I was also on an off label protocol from Care Oncology in the UK, which was a combination of atorvastatin, doxycycline, mebendazole, and metformin. I've cycled off and on the atorvastatin, doxycycline, and mebendazole, because sometimes I feel like I'm having some memory issues, and it's controversial whether or not atorvastatin or mebendazole might contribute to that. I still take Metformin. I have no idea whether or not any of that helps, but it doesn't seem to hurt. Amit Gattani (13:14) Where are you being treated? What is your plan B treatment facility or oncology team? Robert Ellis (13:24) I'm currently being treated at Pacific Cancer Care in Monterey. I live in Carmel Valley. I moved here in the summer of 2020 from San Francisco. I had my original biopsy at Sutter Health. I saw someone at Stanford before I had a scan and realized that I had metastases. I was talking to someone about a possible prostatectomy. And then we got the information that it was too late for that. Then I was in treatment at UCSF in a clinical trial with Dr. Lawrence Fong. I was treated there from 2018 to 2020. And now we're here at Pacific Cancer Care with Dr. Michael Koontz. I was talking to someone at Stanford regarding the clinical trial for Lutetium., but the timing was off. Lutetium had just been approved. So they couldn't put me in a clinical trial, and I couldn't get on it because they didn't have the facility yet to be able to treat patients outside of the clinical trial. And that's when I went on chemotherapy. Mike Yancey (14:55) You mentioned that you were on finasteride (a generic agent that is used to treat lower urinary tract symptoms, complications from these symptoms, and prostate cancer.). When did you stop, and how long were you on that? Robert Ellis (15:00) I'm still on dutasteride (a medication primarily used to treat the symptoms of benign prostatic hyperplasia, an enlarged prostate not associated with cancer). That's for urination, for polyuria (a condition where the body urinates more than usual and passes excessive or abnormally large amounts of urine each time you urinate). I did not try Xtandi (enzalutamide) after Zytiga (abiraterone). There was some controversy. I'm fortunate in that I'm an executive coach. One of my clients is in the cancer space. And they were gracious enough to make an introduction for me to some doctors at MD Anderson and Harvard, and I actually got some free consultations. There were a couple of different recommendations, but the overall consensus was that chemo would be the most sensible next step. So I ended up doing chemo. One opinion was to try some different things, some other ADT to see if I could get any more mileage out of ADT. I did try at one point. In early 2021, after the Lupron was failing, I did a round of firmer gun, which was the most painful experience. I don't know if any of you have been on Firmagon (degarelix, a hormonal therapy). The first round is two shots in your belly. I couldn't bend over for 10 days. It was extremely painful. I didn't respond to it. So that was pretty much the end of ADT, and then Orgovyx became available, and I got on that. Brian McCloskey (16:48) With Firmagon, a lot of it is in the art of how it's administered. The nurse really has to know how to put the needle in. I didn't have quite the reaction that you did, but I had significant bruising. It wasn't it wasn't fun, for sure. Robert Ellis (17:06) I don't recommend Firmagon. Amit Gattani (17:18) Where are your metastases? Robert Ellis (17:24) PET Scan Report PET/CT 9/29/22 1. Persistent increased (SUV 5.2) metabolic activity in the prostate. 2. Only warm metabolic activity in the largest of the bony lesions (left acetabulum and right ischium). The other bony lesions show no activity. 3. No evidence for increased metabolic activity in the previously seen left external iliac chain lymph nodes. 4. This may be secondary to decreased sensitivity of F-18 FDG compared with PyL. This is my PET CT scan report from September of 2022. (This was supposed to be a PSMA test.) It shows persistent increased metabolic activity in the prostate, and metabolic activity in the largest of the bony lesions in the left acetabulum (the socket of the hipbone, into which the head of the femur fits) and right ischium (the curved bone forming the base of each half of the pelvis). There is no evidence of increased metabolic activity previously seen in the left external iliac chain lymph nodes. (The common iliac lymph nodes, four to six in number, are grouped behind and on the sides of the common iliac artery, one or two being placed below the bifurcation of the aorta, in front of the fifth lumbar vertebra.) On an earlier scan, there was just a little bit of activity in the lymph nodes. As far as I know, of course, it may be because this test wasn't as sensitive as the previous one. As far as I know, there's been no progression there. But that's one of the reasons I'm anxious to have a PSMA test. I have had a PSMA test, and so I know that I have PSMA, and I am a candidate for Lutetium. But that's a more sensitive test, and I will have a better idea of whether or not there's been any progression to the disease. It says that there is activity in the prostate, but I subsequently had a biopsy on October 18. They took six cores, three right and three left, and found no evidence of disease, which is kind of a mixed blessing. On the one hand, it may be that I have less of a burden there, but probably not. And unfortunately, it meant that I didn't get any tissue for testing. Caris Report Genomic Features 11/10/2017 Gene/Biomarker Result APCc.3920T>A, I1307K BRCA2Pathogenic, c.5946delT, p.SER1982Ar gfs*22 MSS Stable PD-L1Low (negative) TMB Low TMPRSS2-ERG Fusion A little history about the tissue. This is my Caris report from the original old tissue that was collected November 10, 2017. I have a BRCA2 mutation. I don't know what these other biomarkers mean. I copied them here if anybody knows whether or not any of this is useful, I did a blood draw for the Tempus test where they take the liquid biopsy and compare it to the original tissue. What they found was that my original tissue was not usable, which is another reason why I wanted to get a fresh biopsy, but the biopsy in October was not usable. I'm not exactly sure what happened to the liquid biopsy. At the time Dr. Koontz sa