Keytruda-viable option?: Interested in... - Advanced Prostate...

Advanced Prostate Cancer

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Keytruda-viable option?

HopingForTheBest1 profile image

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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35 Replies
Juliane314 profile image
Juliane314

What's the name of the clinical trial?

HopingForTheBest1 profile image
HopingForTheBest1 in reply toJuliane314

Wasn't told name, and couldn't find on clinicaltrials.gov. Did find reference to it at Journal of Clinical Oncology at ascopubs.org/doi/abs/10.120...

Tall_Allen profile image
Tall_Allen

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.

Bluebird11 profile image
Bluebird11 in reply toTall_Allen

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..

Tall_Allen profile image
Tall_Allen in reply toBluebird11

"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.

Bluebird11 profile image
Bluebird11 in reply toTall_Allen

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...

I appreciate your time... thank you

Tall_Allen profile image
Tall_Allen in reply toBluebird11

There are many clinical trials investigating whether Keytruda may be beneficial if paired with something else.

Terje profile image
Terje in reply toTall_Allen

This paper from Memorial Sloan Kettering was interesting with regards to Keytruda and BRCA2 sciencedaily.com/releases/2...

tango65 profile image
tango65

This article is a good review of DNA Damage Repair mutations and response to immunotherapies.

"Role of DNA repair defects in predicting immunotherapy response"

biomarkerres.biomedcentral....

scarlino profile image
scarlino

There is trial going on that combines Keytruda with Olaparib. I started it in August. Not sure you will qualify but you might ask.

HopingForTheBest1 profile image
HopingForTheBest1 in reply toscarlino

I am aware, but don't qualify since I am already on Olaparib.

scarlino profile image
scarlino in reply toHopingForTheBest1

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.

HopingForTheBest1 profile image
HopingForTheBest1 in reply toscarlino

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.

George71 profile image
George71 in reply toscarlino

how is it working for you?

scarlino profile image
scarlino in reply toGeorge71

Bloodwork is good. I do scans next week so that will tell better. I will update after I get results.

p3d1 profile image
p3d1

Hi HFTB1,

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.

Foundation one CDX test in next on the list.

All the best.

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.

p3d1 profile image
p3d1

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?

HopingForTheBest1 profile image
HopingForTheBest1 in reply top3d1

Low tumor burden and MSS.

I got a "scholarship" from Foundation, which covered most of the cost. On SSD. You should ask them if you qualify for some discount

p3d1 profile image
p3d1

I will check it out but I am in Ireland, probably do not have the same options as you would in the US.

I can cover the cost of the test. The real choice is if I have enough indications to justify covering the cost of 3 infusions of Keytruda.

If my TMB is ultra-mutated because of the Pole snd Pold1 mutations then 9 weeks of “brakes-off” T-cells should have an effect.

At that stage I should know.

Like you my trial options are getting slimmer. Trials want untainted subjects.

After 3 years I have had most types of treatments hence the research of Keytruda.

p3d1 profile image
p3d1

This link specifically relates to BRCA2 and the relationship with immunotherapy.

link.springer.com/article/1...

From the article;

"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.

HopingForTheBest1 profile image
HopingForTheBest1 in reply top3d1

I clicked on the link and it said article not found.

p3d1 profile image
p3d1 in reply toHopingForTheBest1

Just clicked on my iphone and it worked fine. Copy and paste it into google or your browser. It should bring you to the same place.

GAdrummer profile image
GAdrummer

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.

HopingForTheBest1 profile image
HopingForTheBest1 in reply toGAdrummer

What genetic mutation(s) does he have?

How long has he been on Keytruda, and how long is it expected to last? 2 years and done?

GAdrummer profile image
GAdrummer

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.

j-o-h-n profile image
j-o-h-n

Apples and Oranges... Keytruda is working on my lung melanoma..........

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 10/21/2020 6:40 PM DST

HopingForTheBest1 profile image
HopingForTheBest1 in reply toj-o-h-n

And your prostate cancer?

j-o-h-n profile image
j-o-h-n

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...

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 10/21/2020 9:19 PM DST

Chugach profile image
Chugach

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!

HopingForTheBest1 profile image
HopingForTheBest1 in reply toChugach

Great to hear!👍

Vindog29 profile image
Vindog29 in reply toHopingForTheBest1

my husband is msh2 got 2 treatments of keytruda and psa undetectable over 1 and half years. Tumors shrunk and others stayed the same.

HopingForTheBest1 profile image
HopingForTheBest1 in reply toVindog29

Great to hear. Thanks.

Chugach profile image
Chugach

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

HopingForTheBest1 profile image
HopingForTheBest1 in reply toChugach

Wonderful news. Wishing you continued success.👍

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