Back when my cancer journey began I had a battery of genetic tests run, and they all came back negative. However, there seems to be a lot more interest in the subject lately. Did I coincidentally cover all the important tests? These are the tests I had run:
BRC1, BRCA2, ATM, BARD1, BRIP1, CDH1, CHEK2, MRE11A, MUTYH, NBN, NF1, PALB2, PTEN, RAD50, RAD51C, RAD51D, AND TP53
Are you saying that you are positive for BRCA mutations? If so, PARP inhibitors may be useful.
Keytruda is useful if you have MSI-hi/dMMR
Did they do a IHC analysis on the tumor for presence of PSMA, PD-L1, PSA and AR?
No, all the tests as I listed above came back negative. There was no IHC analysis of the tumor that I'm aware of. How long are they required to keep my biopsy samples? I guess I'll need to get up to speed to find out what MSI-hi/dMMr is....
That is usually the case. There are very few genomic markers that are useful for prostate cancer. for MSI-hi, you would have been positive for MLH1, MSH2, MSH6, and/or PMS2 on IHC analysis.
They usually keep the tissue for 5 years. But metastases change over time, so old tissue is pretty useless. Also, genomic testing uses up a lot of tissue.
PD-L1 could be a mutation to study. If it were positive, then the cancer could respond to Keytruda since PD-L1 is blocked by this drug. The best choice is to have a direct biopsy if possible or a liquid biopsy. since the cancer changes with time and an actual determination of the somatic genome could be more useful than using old tissue.
So far, Keytruda has been proven effective for Non-Small Cell Lung Cancer with PD-L1. That's a good sign so far.
I finished my Provenge treatment in June so I've already hit it once on the immunotherapy front. Is Keytruda recommended afterwards?
Keytruda is approved for many cancers, some of them require to have specific mutations:
drugs.com/history/keytruda....
Prostate cancer could be included in the following group if the somatic genome shows these mutations:
"Keytruda (pembrolizumab) is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs."
fda.gov/news-events/press-a...
More recently they extended the approval which could include PC:
"On June 16, 2020, the Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co., Inc.) for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options."
fda.gov/drugs/drug-approval...
The approvals mention PD-L1 somatic mutations, for NSCLC, urothelial carcinoma, gastric, esophageal and cervical cancers.
accessdata.fda.gov/drugsatf...
Keytruda specifically blocks PD-L1. If I had a cancer which is PD-L1 positive I would consult with MOs to see if it is indicated to be treated with Keytruda.
I believe than having provenge is not a contra indication to use Keytruda.
Best of luck!!
Sometimes there is somatic mutation. That happened to me and might allow you to enter immunology clinical trials or treatments that you could not qualify for early on.
What does somatic mutation mean and how do you test it?
It is a mutation that occurs after conception so you are not born with it. I don’t know the answer to that for sure. How I was told is when a second genetic test was performed on me, a new mutation was identified that was not identified in the first test.
I'll bring these topics up with my local MO next week. I would suspect that Dr. Scholz is up to speed on all this, but I don't speak with him again for a couple of months.
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