Nivolumab+docetaxel trial: Hello, After... - Advanced Prostate...

Advanced Prostate Cancer

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Nivolumab+docetaxel trial

Catfish21 profile image
16 Replies

Hello,

After ADT +Zytiga treatment, my cancer became castration-resistant. My MO suggested me to participate in Nivolumab/placebo + docetaxel trial, Phase 3. I checked the results of Phase 2, and, honestly, I was not very impressed with results. I found no big difference between effectiveness of this combo and docetaxel only. Did you hear something about more encouraging results on this combo? My cancer cells do not have heritage mutations. Thank you.

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Catfish21
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16 Replies
Tall_Allen profile image
Tall_Allen

I thought the Phase 2 results looked good (not great, but good) - 40% of treated patients achieving a confirmed objective response and almost half achieving a ≥50% PSA decline from baseline. What is interesting is that good results were realized even in heavily pretreated patients, and even if they did not have the genomic characteristics usually associated with a good response to checkpoint inhibitors.

Catfish21 profile image
Catfish21 in reply toTall_Allen

Thanks a lot Allen for your reply.

Seasid profile image
Seasid

"He recommended me to go with Lupron only. In 2019, Lupron stopped working (PSA=33, multiple metastases in bones), and MO added Zytiga in 2020." I would like to understand why did they wait so long to introduce Zytiga. I am not a doctor nor I have experience but I would want them to introduce something new (like Zitiga) much earlier than to wait for a PSA to rise to 33. Can you clerify this?

Catfish21 profile image
Catfish21 in reply toSeasid

The same situation, Seasid. My MO prescribed Zytiga when my PSA reached 33, and I got multiple metastases in the bones.. Zytiga lowered PSA to 1.9 and decreased the number of mets. But it stopped working in 1 year. Now I try to find the appropriate trial.

Seasid profile image
Seasid in reply toCatfish21

Are you still with MD Anderson?

Catfish21 profile image
Catfish21 in reply toSeasid

Yes, I live close to Houston.

Javelin18 profile image
Javelin18 in reply toSeasid

I think there's a general tendency with SOC based MOs to avoid combined treatments that haven't been tested in trials. From my discussions with my MO, they are concerned that an unknown toxic side effect will show up.

There also seems to be a bias towards prolonging life ny getting base hits from sequencing individual treatments, rather than swinging for the fences and trying to get a cure with combined therapies. This is in line with the hypocratic oath of first do no harm, but is much slower way of finding a cure.

There's also a division of labor in oncology. Research MOs test hypotheses, clinical MOs apply the research.

Seasid profile image
Seasid in reply toJavelin18

My MO proposed to put me on medical trial when my PSA reaches 1. I will go either to get Zytiga or Zytiga + Olaparib. I would still stay in addition on ADT. My last PSA was 0.39 on Degarelix, Metformin, Crestor 40mg /day and doxycycline 100 mg per day. In April I will celebrate 4 years since I was diagnosed. I may do a psma pet scan when my PSA reaches 0.5, but I am not sure yet. I don't have bone pain, only intermittent nerv pain. I have bone metastasis mainly in my spine etc.

Javelin18 profile image
Javelin18 in reply toSeasid

I've joined the CAR-T trial at City of Hope, which targets PSCA. I'm waiting for phase 1B to start in a couple months. I was denovo mCRPC at diagnosis, so my PSA spikes at the end of each SOC treatment. I'm on cabazitaxel while I wait for the trial to start. PSA dropped a bill to 264 after the first cycle of treatment.

Not trying to be a topper, just hoping my readings give you some comfort that yoous are still low.

Seasid profile image
Seasid in reply toSeasid

I stopped using everything except Firmagon (Degarelix) injections. My PSA is 0.75 now (we are in July 2022 now). Up from 0.65 a month earlier. When my PSA get to 1 i will try to get a PSMA PET scan if they want to give it to me. I an not even sure that I can get a clinical trial now as my prostate biopsy sample was rejected by PeterMac. They are not good enough quality samples for genetic testing. My Gleason score is 7 (4+3). I stopped after 6 months doxycycline as I was afraid that I developed intacranial pressure. I stopped statins to take a drug holiday. I stopped metformin as I really hate this drug. And I stopped aspirin as I am afraid of bleeding. I am 64 this month. Aspirin can cause bleeding by the 70 years and older, plus maybe it is not effective anymore. I just wanted to see how my PSA will go without all of these drugs. Only on ADT (Firmagon) since my diagnosis and I had early chemotherapy. Nadir was PSA 0.12

Javelin18 profile image
Javelin18

Can you post the link to the phase two results? I'd like to to comment directly on them.

My general impression is that checkpoint inhibitors don't produce great results in solid tumors, unless there microsatelite instabilities or gene repair mismatch defects. Checkpoint inhibitors affect the regulatory mechanism of T killer cells.

After discussing this with Dr Aparicio, it seems that other immunosuppressive macrophages and T cells are responsible for stopping the immune response. Unfortunately, the research community doesn't seem to know which components are responsible for it.

Catfish21 profile image
Catfish21 in reply toJavelin18

The link is below, but it looks that this study was done, in general, to increase nivolumab market. Nivolumab alone is low effective for PC. Factually, only 3 phase will answer if the addition of nivolumab to docetaxel will be more effective than docetaxel alone.urotoday.com/conference-hig...

GeorgeGlass profile image
GeorgeGlass in reply toCatfish21

Did you read the mouse study that showed creatine and nivolumab together showed very good results?

Seasid profile image
Seasid

You didn't have docytaxel chemotherapy yet. Can you do 4 to 6 cycles if your health status allow that and then start with enzalutamide? I would try that before getting more experimental by taking part in clinical trials? I would also get into provenge if I could. I believe that you did so well untill now manly because you had provence before. You could maybe just simply stay with abiraterone and change prednisolone to dexamethasone. Maybe it will work for you? The best would be chemo and then enzalutamide.

Catfish21 profile image
Catfish21

Thanks a lot guys for your responses.

Seasid profile image
Seasid in reply toCatfish21

Why they didn't give you Zytiga much earlier?

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