Not a candidate for the CAR-T trial. Should I pursue cabozantinib here in the USA or look abroad for LU-177?

[Cleodman]

Unfortunately I received some bad news this week. Since I have a seizure disorder I am no longer deemed a suitable candidate for the CAR-T trial which I was planning on participating in at the City of Hope in Duarte, CA under Dr. Tanya Dorff. CAR-T can have some serious neurological side effects such as encephalopathy and seizures. Even though I am controlled with anti-convulsant medication they did not want to put me at risk. Most of this decision follows a bad outcome (death) of another patient who was infused with CAR-T for leukemia at COH just a few months ago.

So...

I promised my significant other that I would try one more clinical trial. Do any of you have any experience with either of these.

The Mayo Clinic has accepted me to get either cabozantinib (XL184) alone or in combination with atezolizumab (immunotherapy). Cabozantinib is an oral agent which is great and is FDA approved for medullary thyroid cancer. This is a phase 2 study.

The other treatment that has caught my eye is LU-177 offered in India and Germany. Of course you need to have the PSMA receptor for this to be effective but I hear some really good regression is a number of men who have castration resistance and who have failed docetaxel.

Any thoughts brothers?

[Faith1111]

Have you been tested for mutations?

[Cleodman in reply to Faith1111]

Yes. I have no suitable mutations or none that are know for current therapeutic intervention (ie Keytruda)

[ScottfromSD]

Cleodman, I’m now 6 months into the Cosmic 021 trial (Cabo + Atezo). The scans have been relatively stable with no new mets visible on ct or bone scans. The side effects from the Cabo (diarrhea & nausea) got a bit brutal so my MO reduced the dose and I’m doing much better. Keep in mind that these drugs do not impact psa so you will likely see your psa rise during treatment - this is obviously disconcerting. Let me know if you have any more specific questions.

[Cleodman in reply to ScottfromSD]

Did your previous mets shrink at all? Why would these treatments not affect PSA if the disease regresses from treatment?

[ScottfromSD in reply to Cleodman]

No evidence that previous mets have shrunk. For me, the purpose is control and stability of the disease. As to psa, no impact the same way Provenge has no impact.

[Tall_Allen]

I'm sorry you didn't qualify for the trial you wanted, but CAR-T can be dangerous. Did you discuss BiTE with Tanya Dorff?

Cabozantinib (Cometriq) has been around for a while. I remember when it was touted as the hot new therapy for prostate cancer (Eugene Kwon did a big presentation on it in 2012 at PCRI). Unfortunately, it didn't live up to its hype, at least not as a single agent for prostate cancer:

ascopubs.org/doi/10.1200/JC...

sciencedirect.com/science/a...

However, hope remained that it might be beneficial as an adjuvant therapy along with something else. An early trial of it combined with atezolizumab showed some activity:

meetinglibrary.asco.org/rec...

One of the problems with ascertaining its effectiveness is that it may create a false negative on bone scans and PSA may not be a good indicator of its effectiveness. If you are randomized to Cometriq alone, you know that it will probably not be effective.

There are some trials of Lu-177-PSMA in the US that you may want to look into before traveling abroad:

prostatecancer.news/2020/08...

[MateoBeach]

Practical approach for your consideration: Go get a PSMA PET scan such as at UCLA ( private pay about $2700). If you have high PSMA avidly mets the lean towards Lu PSMA treatments first in Australia India or Germany. If no or low avidity then no sense bothering with these. Trial of your selection could follow.

[Cleodman in reply to MateoBeach]

Thanks. Yes that is the plan I am pursing. I opted out of the other trial as I am only interested in targeted therapy from now on.