Olaparib Combo Improves PFS/Responses in Metastatic CRPC - from ASCO GU2024

[Maxone73]

I am not sure, they always mix BTCA 1/2 and ATM, but maybe I can find the data for ATM only...but results are impressive from the report.

cancernetwork.com/view/olap...

[KocoPr]

it says it’s for BRCA 1/2 OR ATM

[KocoPr]

here is what the trial inclusion says. Kind of vague but im sure one can find the exact mutations somewhere.

From clinicaltrials.gov inclusion criteria #3

#Patients with known germline DNA repair defects are eligible without a biopsy. However it will be highly desirable that they undergo a metastatic (or fresh prostate biopsy if there is clear local disease and no other measurable disease site or biopsiable bone lesion) disease biopsy to better define the scope of the DNA repair defects in the current disease context.”

[Maxone73 in reply to KocoPr]

yes but there are trials saying that olaparib works greatly on BRCA 1/2, so-so for ATM and basically does nothing to people with no mutation, that's why it's tricky

[KocoPr in reply to Maxone73]

Ya I tried to get into the rucaparib trial at Wiel Cornell but my RAD50 mutation was label VUS (variable of Unknown Significance) in prostate cancer. it’s a ver very serious mutation in the BRCA pathway and is well known for colorectal cancer and breast cancer.

oh by the way I am so glad i wasn’t excepted at last minute after traveling 4 hours to NYC, going through all the radiation scans bone, cat, etc, and then surrounded by Homeland Security at Penn station because i set off the radiation detectors. Lol

[Maxone73 in reply to KocoPr]

I am ATM mutant instead, dammit

[MoonRocket in reply to Maxone73]

Correct, your are a ATM Mutant. 😀

[Maxone73 in reply to MoonRocket]

And no ATM machine at home!

[MoonRocket in reply to Maxone73]

FWIW, me neither. 😒

[MoonRocket in reply to Maxone73]

I believe the reason that tissue biopsy is being used instead of liquid biopsy is the high false positive for ATM. I've listened to a few MO discuss the this issue with regards to ATM response to Parp inhibitors. Some, number unknown, ATM participants did not actually have an ATM mutation. Need to read the more detailed reports from this study to see if anything has changed if tissue biopsies are used.

[Maxone73 in reply to MoonRocket]

That would be interesting! I had a repeated blood test for this germline mutation, now I have two sisters and one brother that will have to do the genetic test as well.

[Maxone73 in reply to MoonRocket]

I know there was a reliability issue with home kits nature.com/articles/gim201838

But I did not know about hospital tests

[MoonRocket in reply to Maxone73]

Read this...ancan.org/liquid-biopsy-tes... explains the issue and how to weed out the false positives.

[Maxone73 in reply to MoonRocket]

Interesting… I know they used a double blood sample taken from a different arm, taken 15 minutes from each other and done by a different nurse. But I think that was an internal protocol. I must check if they used plasma or whole blood!

[MoonRocket in reply to Maxone73]

My ATM was from my prostate tissue post RP, so my ATM mutation started from the beginning, which is pretty rare from what have read. Anyway, I don't think this false positive was understood when olaparib was first approved. I also think this issue is more common for ATM than the others.

[Maxone73 in reply to MoonRocket]

I will find out the report to see if the method is specified and its sensitivity! But they told me they will repeat the test anyway.

[MoonRocket in reply to Maxone73]

Germline test would be different in that every cell would be impacted. Usually the germline test are saliva based but don't quote me on that. I'm not a genetic counselor.

The liquid biopsies use material that is shed from the cancer although some is not exclusive to the cancer, hence the issue with some liquid biopsies.

[MoonRocket in reply to KocoPr]

I won't put my hand on the Bible, but not all Gene mutation are equal, even within the HRR set of genes. I think there are specific mutations within each gene that are significant while others Variants are Unknown, therefore the VUS designation.

[Maxone73]

😂