Interested in hearing experiences with Keytruda. My Oncologist is suggesting a clinical trial for BRCA2+ and MSS patients, which I have both.
Have been on Olaparib for over a year and a half, during most of that time controlling my PSA as undetectable. PSA has now been rising for the past 3 months, up to 0.68 currently. Continuing on Olaparib for now, but will probably need new treatment sooner than later. Oncologist not too anxious to change therapy at this point, since my recent scans were clear.
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HopingForTheBest1
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You don't want to give up on something that's still working - your PSA is low and no new metastases is great! Keytruda has not been effective unless one is MSI-hi/dMMR.
I'm about to enter the immune/gene arena. I don't have a better way to say it.
I've been able to help my husband and stay fairly current with things up until a few years ago.
Is there some way I an understand your MSI-hi/dMMR statement above.
We did 23&me some years ago. I can pull that out. Then in 2018/19 my husband had a biopsy with an integrative radiologist. He sent the biopsy to Foundation One. I now am just sitting in a boat with no engine. I need to step in again. I began this journey at 64 and now moving soon to 78, it's just gotten harder, yet sincerely grateful ... I must focus in on this area. It's integral not to rule out or rule in options.
BTW, we did use your referral to Boyyanouski. We like him. Thank you..
"Is there some way I can understand your MSI-hi/dMMR statement above."I'm not sure what it is you don't understand. Keytruda has been shown to have no activity against PCa when used as a solo agent. The exception is a rare genomic trait known as high microsatellite instability (MSI-hi) and defective DNA mismatch repair (dMMR). If the Foundation One report identified MSH2 mutation, he might have it. But as I said, it's rare.
Okay.. well, that's an answer and a help towards understanding. Prior to you saying this, I had zero idea of this *MSI-hi being rare and that Keytruda has shown to have no activity against PCa when used as a solo agent.
I listened to a couple of PCa oncologists who never mentioned this except he's seen it work, he's seen it not work- side effects could be lasting and reported on that type of information. That leads a patient to believe they could be in the camp giving it a shot of working...
So, thank you.. I will look at the Foundation One report.
I appreciate your get to the point position- it helps not having to wade through a bunch of weeds...
Might your doctor prescribe Keytruda too since it’s an FDA approved drug? Insurance may balk since it’s not approved for prostate cancer but it is a possible way to take both. Of course that may not be possible.
My understanding is that it is not possible. As you said, Keytruda can only be used for PC in a clinical trial since it is not yet approved. Hence, the reason for the trial.
Hope the trial goes ahead for you. I also have a BRCA2 loss and am researching Keytruda. Rubraca worked for 9 months so there is a HRR loss. Also have PALB2 and ATR mutations so it could easily be either of those.
Tango65’s article gives some indication of the way biomarkers are going with immunotherapy.
It is better I think to look for multiple hits. i.e. PD-L1 and TMB and HRR and MSS.
It is a bit of a lottery when genetic testing but it is the future if you have the right combination.( or bad combination depending on how you look at it)
I looked back over my trial genetic test after Rubraca stopped working. It turns out that I have a Pole and Pold1 mutation as well. Probably a 1 in 500 chance of a double hit.
If you haven't had the Foundation test yet, what genetic test did you have that identified your mutations? I had the Foundation test after my prostatectomy, and a tissue sample was harvested. I also had the Color spit test. Both confirmed BRCA2.
I had the foundation medicine test as part of the Triton 3 trial but it was trial specific. 395 gene panel looking for BRCA1/2 or ATM. It only reported on gene mutations.
The BRCA2, PALB2 and ATR were found in a TURP biopsy but not in the blood so I had a Somatic loss not Genetic. This is why I believe I had no side effects while on Rubraca even though my tumor shrunk by 50% .
I need the foundation one CDX to look for MSS and TMB, I will add the PD-L1 test as an option. Should cost approx 7000 dollars.
The results will inform if I try Keytruda.
Did your test indicate TMB? Or did it indicate for any other HRR mutations?
"Preliminary data from a phase II trial of the anti-PD-1 antibody pembrolizumab in 258 patients with docetaxel-refractory mCRPC showed a 5% objective response rate (ORR) regardless of PD-L1 status, but an ORR of 12% in patients with somatic BRCA1/2 or ATM mutations [25]. The latter finding is in line with results, showing that BRCA2 mutations are enriched in melanoma patients responding to anti-PD-1 therapy [26]. Since HR deficiency causes increased mutational load thereby potentially creating neoepitopes, it could be used to define a subgroup of prostate cancer patients who would potentially benefit from immune checkpoint inhibitors."
This is why I believe that using a single biomarker may not be the best option.
A combination of different possibilities may give the best "index" of the chances of success.
Our medical oncologist tried all the usual treatments for lymph node only mCRPCa, stalling while waiting for new treatments to become available for my husband's mutations. He kept Keytruda in his back pocket and pulled it out when nothing else appeared. We don't know how/if approval was obtained. [compassionate use?] We have not had to pay for Keytruda, so it may be some "in house" 2 yr. trial. On it, an undetectable nadir was reached for the first time. That success came with a cost: the destruction of his adrenal and thyroid glands. [a rare side effect, but his version of PCa is rare] So when the MO gave him a flu shot last week, the next day he started crashing, so the hydrocortisone had to be doubled. OK now, but it was a scare.
He's been on it for 15 months. Because of Covid-19, he is getting the second year doses at 6 week intervals. Then we'll see what happens next. I have not been allowed to go with him to appointments due to Covid-19 restrictions, so have not been able to clarify the genetic markers situation. Even tho his mother's line died of breast cancer, BRAC-1/2 were not in his liquid biopsies. Early on none of the "usual" mutations were found. He's a rarity, exceptional in many ways.
Both my Pca MO and my Melanoma MO said that unfortunately there is no benefit for my Pca while taking Keytruda. I know.... two for the price of one would be a great bonus...
I’ve been on Keytruda for a year now, starting my PSA was 122, now it’s been undetectable since a few weeks after starting. All my bone mets are healing and I feel great. I was MSI-H. Hope it works for you!
I was on the ropes and out of options then a Hail Mary (genetic testing said I was MSI-h = Keytruda as an option). After 2 Infusions PSA was Undetectable and it’s been over a year now- undetectable and Mets all healing
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