ATM gene mutation

[Rfs1975]

I just received results from genetic testing that I have a ATM gene mutation. I am currently not on any meds and my last PSMA pet scan was negation. I am scheduled for a follow up PSA test mid march based on rising PSA after 5 years undetectable. Based on the ATM finding will this change any future therapy.

Richard

[Tall_Allen]

Sadly, there are no treatments for ATM mutation. Olaparib is approved, but results are minimal and it is very toxic. The best response is to docetaxel:

onlinelibrary.wiley.com/doi...

Discuss adding carboplatin too.

[Rfs1975 in reply to Tall_Allen]

Thanks Tall Allen for the excellent article. Would these treatment precede ADT or would they be used prior to ADT. Currently, I am not on any medication but waiting for a follow up PSA test in March. I appreciate your expertise and feedback

Richard

[Tall_Allen in reply to Rfs1975]

Always after or along with ADT.

[Rfs1975 in reply to Tall_Allen]

I was hoping to avoid the ADT but I guess that is not an option

[dhccpa in reply to Tall_Allen]

TA, since chemo is systemic and kills fast dividing cells, why isn't it used up front in an attempt to kill everything? And why would that not work? Are different types of PCa cells simply unaffected by docetaxel?

Thanks

[Rfs1975 in reply to dhccpa]

Interesting question

[Tall_Allen in reply to dhccpa]

It is used upfront in newly diagnosed metastatic men as part of triplet therapy.

[dhccpa in reply to Tall_Allen]

Yes. Any chance it conflicts with ADT to some degree? Their mechanisms clashing?

[Tall_Allen in reply to dhccpa]

No- they work together in triplet therapy.

[dhccpa in reply to Tall_Allen]

OK thanks

[Shorehousejam in reply to Tall_Allen]

What about this?

Is this trial before or after the above article, so I would need to do docetaxel again?

Olaparib has demonstrated preliminary efficacy in metastatic castration-resistant prostate cancer. In a trial of 49 evaluable patients treated with olaparib, 11 / 49 experienced a PSA response, and every patient with a radiographic response also had a PSA5 response. Ten of 11 responders had mutations in DNA repair genes. While PARP inhibition is showing promise in these initial studies, reserving its use for end-stage patients may not be the optimal timing for olaparib therapy in some patients. In addition, PARP enzymes function in roles beyond DNA repair, and specifically for prostate cancer are involved transcriptional regulation of the androgen receptor. PARP inhibition has not been tested in earlier disease states for prostate cancer.

Related Conditions:

Prostate Adenocarcinoma

Prostate Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

clinicaltrials.gov/show/NCT...

[Tall_Allen in reply to Shorehousejam]

So far, olaparib has not benefited men with the ATM mutation specifically. It does benefit men with BRCA mutation. Perhaps it might if used earlier in non-metastatic, recurrent men. But we just got some good therapy results for that group from the EMBARK trial. Enzalutamide is a lot less toxic than olaparib.

prostatecancer.news/2023/05...

[Shorehousejam in reply to Tall_Allen]

Thank you, I’ll tag you under my post for further discussion if you don’t mind

[Rfs1975 in reply to Shorehousejam]

Thanks for the article

[Maxone73]

they are working on ATR inhibitors for ATM mutations, they work better than PARP inhibitors like Olaparib.

[Maxone73]

like this: pharmaceutical-technology.c...

[Rfs1975 in reply to Maxone73]

Hello Maxone,

Thanks for the feedback, greatly appreciated

[Maxone73 in reply to Rfs1975]

we are ATM brothers after all!! 😆

[Rfs1975]

I'm keeping good company!

[Maxone73]

😜

[tango65]

I f your PSA is not increasing and the scans are negative I believe it is not indicated to do anything. If there is evidence of radiographic progression or a very fast PSADT in 2 or 3 PSA measurements you will have to discuss possible treatments.

Your are been treated in one of the beat places in the country, they will know what to do to control the cancer.

This is a phase 3 trial showing the poor response to Rucaparib of cancers with the ATM mutation

nejm.org/doi/pdf/10.1056/NE...

[Rfs1975 in reply to tango65]

I agree. My PSA has went from undetectable for 5 years to 0.1 in July to 0.4 in December. PSMA pet was negative, retesting PSA on March 15th.

[tango65 in reply to Rfs1975]

I wish you the best of luck!!!

[Rfs1975]

Thanks Tango65

[MoonRocket]

Discuss the EMBARK Trial. It was recently approved and I think you'd do well on it.You don't specify if you have germline ATM or somatic and I'm assuming it's germline.

I have somatic ATM loss and I am on ADT + Xtandi. After 39 weeks if PSA is < .2 you can stop until it reaches 2. Very good results for metastasis free survival.

[Shorehousejam]

I have a ATM Frameshift Mutation

[witantric]

In my experience oncologists at NIH are the most upto date with clinical trials. Is it possible to get a consult with one of them?