Molecular Tumor Board for Advanced Prostate Cancer Treatment Options

A Hackathon (Molecular Tumor Board) for Advanced Prostate Cancer Patient and Cancer Researcher Dr. Elliot Davis” Brad Power and Gabrielle Ruvinsky September 25, 2024 “I'm at the point where chemotherapy is losing effectiveness, although it still works somewhat.

” – Elliot Davis “You're in a position now that I think you need to go to a cancer center that has a lot of trials, like ours, Sloan Kettering, Mount Sinai, Johns Hopkins, Fred Hutchinson, UCSF, something like that, where you're going to have access, and not only access, you're going to have doctors that are going to think outside.

Because I know what trials we have here, but I have access to those other doctors, so that when I see them next week at one of the conferences, I'm going to be like, ‘Hey, I got this patient. Do you have a trial for him?

Advanced cancer patients often have relatively easy decisions at diagnosis. There is a standard treatment -- maybe surgery, chemotherapy, or radiation, or some combination -- with a high success in getting a complete response. Increasingly the treatment landscape may also include drugs that are targeted to your unique genetic mutations. If you're lucky, there is an immunotherapy with a high response rate and durable response.

But as the options increase, your treatment selection decision gets more difficult. Newer treatments have less of a long-term track record. And the more rounds of treatment you receive, the more complicated the decisions about your next treatment become. Dr. Elliot Davis is in a predicament. He is a stage 4 (metastatic) prostate cancer patient, who has been battling the disease for over eleven years. He is 79, and was diagnosed when he was 69.

He is on his seventh line of treatment in eleven years. His PSA has been in the 0 to 400 range, but is now in the 5 - 15 range. His metastatic lesions are probably mostly in his bones, which are painful and hard to biopsy. After getting Pluvicto (a new drug that grabs onto prostate cancer cells and delivers a radioactive payload), the cancer spread to his liver.

However, the liver tumor was resolved after switching to cabazitaxel (a chemotherapy treatment used to treat advanced prostate cancer that has spread to other parts of the body), and it seems it may be losing effectiveness. It is awful stuff, with terrible side effects. He also is getting Orgovyx (Relugolix) which lowers testosterone. He probably will soon have to try some less standard therapy.

The treatments have sequentially provided relief for less and less time. Why is Elliot’s treatment decision difficult? Prostate cancer has benefited from a continuous stream of available treatment options. For example, “radioligands” which bind to unique receptors on prostate cancer cells have become available in the last two years. But these new therapies add to the complexity of choosing those treatments.

Some advanced cancer patients find that they don't get durable responses from any treatments, and their condition continues to deteriorate. They need to identify new treatment options while also dealing with side effects, weakening health, and blows to their resiliency. How have others made these complex treatment decisions?

Elliot Davis” Our spiritual founder of the Cancer Patient Lab, Bryce Olson, faced a similarly difficult decision in December 2020. Bryce told his friend Brad Power that after seven years and eight rounds of therapy for his metastatic prostate cancer, he had hit a wall and feared that he had run out of treatments that had a chance of knocking down his cancer.

As cancer patients like Bryce try more and more lines of therapy, they look less and less like other patients, and they get farther away from treatments that have solid evidence to support them. In January 2021, the urgency for finding a solution increased as Bryce’s prostate-specific antigen (PSA) test (a measure of the activity of the prostate cancer) spiked up.

By mid-January he also presented with radiographic progression as measured by novel (“PSMA-PET”) scans at UCLA along with conventional imaging at UCSD – all indicating that his cancer was being more aggressive. Brad suggested that they could organize a hackathon – a collective effort to find out what was driving Bryce’s cancer and stop it.

By engaging a broad community of experts with diverse experience, they hoped to identify new molecular drivers and biomarkers along with treatment options that could complement ideas from Bryce’s extremely talented oncologist. Their goal: Get Bryce his next treatment in a couple months. Bryce put his extensive medical data and reports in a cloud repository and permissioned access to anyone who wanted to review it.

The collaborative effort achieved its goal to help Bryce and his medical team decide on his best next treatment. The PSMA-targeted radionuclide therapy which was chosen was not on Bryce’s list of treatment options going into the hackathon.

The main benefit of the hackathon to Bryce and his medical team was greater confidence in that selection, and the consideration and upgrading or downgrading of other options, which may be useful if a next round of treatment is needed. What was the advice that Elliot received regarding his decision on his next treatment?

Brad Power This is the Cancer Patient Lab. I'll do the housekeeping chores before we get started with our honored guest, Elliot Davis. This is not medical advice. This is information which we hope will be useful for you to bring to your medical team. We are a nonprofit patient-led community, so we welcome any donations you might be inspired to give, which you can do at our website, at Cancer Patient Lab.

Brian McCloskey 1:00 Elliot, it's nice to meet you. Today's session is a little bit different than most of the ones that we have – a mini hackathon where you're going to present your case as a stage four metastatic prostate cancer patient who's gone through seven lines of treatment – or is on your seventh line of treatment right now.

Our intent is to be able to get insights from the community, specifically those on the call today in terms of their experiences that may have a bearing on your treatment plans. When I read your bio, I could certainly relate – I am also an advanced metastatic, castrate-resistant prostate cancer patient. I've gone through many of the lines of treatment that I think that you've gone through. Elliot Davis 2:24 Thank you very much.

I'm at the point where chemotherapy ( cabazitaxel) is losing effectiveness, although it still works somewhat. The PSA goes down when I get the treatment, then it goes up again. Eleven years ago, I was first diagnosed with prostate cancer. It was all over my body. I had tumors all over, including the neck and back, and they recommended a large amount of radiation to get rid of the tumors. Just androgen deprivation therapy - it worked marvelously.

But it wore off after a while, and they tried subsequent treatments that still were aimed at the testosterone antigen at ADR (androgen receptor), at the antigen deprivation axis. Eventually all of them lost effectiveness. About a year ago or so, they recommended cabazitaxel, and it worked very well initially, but it's starting to lose effectiveness. The side effects are horrible.

I've lost probably 60 pounds, and there’s nausea and an inability to eat. Elliot Davis” Here's the graph showing my PSA while I've been getting cabazitaxel from June 21 to now. The PSA is rising, although it still has some effectiveness. It would be wonderful to get into some sort of a trial, or find some sort of an alternative treatment. I haven't found anything that looks overly promising.

One month ago I got a blood sample from Advent Health, on September 4, a Foundation One test. I didn't hear anything. I called around, including Foundation One, and they knew nothing about this. Finally, this morning I got a call saying that they sent the sample to the wrong people. They didn't send it to Foundation One. Also they sent the wrong people the wrong instructions.

So being obviously a very responsible group, they canceled everything, and now I am here without any genetic results at all. I have genetic results about a year ago, which Dr. Subudhi has seen, which shows some efficacy with PARP inhibitors (PARP inhibitors block PARP, which helps repair damaged DNA in cells. This prevents cancer cells from repairing their DNA, causing them to die. ), but that's about it.

So the way I see it, my only decent option now is to get on some trial, and if you people know of any, or can suggest some sort of alternative treatment that's realistic I would love to hear about it. I do cancer research myself, and we do have some promising results with prostate cancer, but we can discuss that later. Do you have any suggestions? Brian McCloskey 7:48 I see that Dr. Subudhi is on so he may have some thoughts.

Elliot Davis” I'm going to give you a suggestion that isn't related so much to treatment right now, but is really related to your current condition with cabazitaxel. I started cabazitaxel two and a half months ago. I just finished my fourth round of it. I'm combining it with carboplatin, but I've lost about 13% of my body weight. So that's not as much as you, about 25 pounds. In the last three weeks or so, I started a medical grade probiotic.

I don't know right now whether or not it's completely working, but it seems to be. I'm five or six days out from my last treatment, and my stomach is fine. I don't really have diarrhea or anything like that, which is just really poor for keeping your weight on. Since I started this, I've gained about eight pounds back. I'll put in the notes here the link to the medical grade probiotic that I am using.

I'm also doing something that I've never done, which is counting my calories. So I have an app that is, counting my calories, making sure that I get at least 2400 calories a day. , I'm really touching on something that is important for you to get to your next treatment, which is to maintain or to improve your existing health. You can't take on some of these drugs unless you're physically fit and healthy to be able to take it on.

I don't know the research behind the probiotics. I know there has been some research recently about the effect that chemo has on the gut microbiome, but this probiotic does seem to be working. I'll put it in the notes for you. There have been a number of questions that have come into the chat. The first is from Dr. Subudhi, and it requests a list of prior therapies. Do you have those? Joe Davis 10:38 This is Joe, Elliot’s son.

I'm going to share my screen: “A Hackathon (Molecular Tumor Board) for Advanced Prostate Cancer Patient and Cancer Researcher Dr. Elliot Davis” Joe Davis 10:48 He started out with intermittent Degarelix (a drug that decreases the amount of the male hormone testosterone produced by the body). This may slow or stop the spread of prostate cancer cells that need testosterone to grow back in 2013 and was on that until 2018.

In 2018 I switched to Zytiga (abiraterone, a drug which blocks the body's production of testosterone), intermittently until 2020 and then Nubeqa (darolutamide, a second-generation hormone therapy that blocks the activity of testosterone inside cancer cells). There was some radiation. We opted for a stereotactic, curative dose as opposed to palliative.

Originally, the physicians wanted to do palliative treatment, and Elliot requested curative treatment instead. Of course, it doesn't wipe out the cancer everywhere, but where it's hitting, it does, and that actually worked extremely well for a while. So we were playing whack-a-mole with the radiation. Then in 2022 he got one round of docetaxel (a chemotherapy), and then switched to cabazitaxel (another chemotherapy) immediately afterwards.