Ipatasertib+abiraterone effective in men with PTEN-loss

[Tall_Allen]

As genomic breakdown continues in prostate cancer metastases, PTEN, a tumor suppressor gene, and the protein it makes, is often lost. PTEN deletion is common even early (18% of prostatectomy samples). Without PTEN, the cancer cell signals proliferation with a chemical called AKT. Ipatasertib inhibits AKT. A large Phase 3 trial found that ipatasertib combined with abiraterone significantly increased radiographic progression-free survival by 2 months in men who were previously untreated, metastatic and castration-resistant with PTEN loss.

But ipatasertib is quite toxic -70% suffered serious or worse adverse events, and 21% discontinued taking it.

thelancet.com/journals/lanc...

For those who know they have PTEN-loss and who want to try a similar medicine while waiting for FDA approval, another AKT inhibitor, capivasertib, is currently recruiting in randomized clinical trials:

clinicaltrials.gov/ct2/show...

[carbide]

Interesting, but above my pay scale.Keep your good information comming,

will help some.

[StayingOptimistic]

I can’t believe all the time you spend researching these things. We truly appreciate your help. Thanks for posting it.

[tallguy2]

Thanks for posting this. A difference in median progression-free survival of 2 months doesn't sound like much unless the patient is in the upper half of survival for the men on the study drugs. All of this work is definitely headed in the right direction.

[Tall_Allen in reply to tallguy2]

PTEN loss has a poor prognosis so 2 months is pretty good for that patient population. As you say - in the right direction.

[tallguy2 in reply to Tall_Allen]

Yes, my tumor biopsy showed PTEN loss so I've been following this with great interest. But I've had much treatment in 9 years so the drugs aren't for me. Nonetheless, I'll review the article with my oncologist on Friday. Thanks.

[Tall_Allen in reply to tallguy2]

You raise a really good point about when PTEN loss occurs,. If it occurs early (like in those 18%), there is much more time for out-of-control proliferation to occur, If it occurs much later, it may be less destructive. I guess that's why they selected men for the clinical trials who had not been through a lot of treatments yet - they have the most to gain.

[StayingOptimistic in reply to Tall_Allen]

Just a quick question please, does PTEN shows up on a somatic gene analysis or Germline one?

[Tall_Allen in reply to StayingOptimistic]

They used IHC to detect the lack of the PTEN protein. Somatic genomic testing can discover the loss of the PTEN gene that codes for the protein. Germline loss would be exceedingly rare.

[Jmr11820 in reply to Tall_Allen]

Do you know if DECIPHER shows PTEN loss? Possibly the GRID?

[Tall_Allen in reply to Jmr11820]

It does not. IHC is best because unless the loss is biallelic, you will still make the protein.

[Jmr11820 in reply to Tall_Allen]

Appreciate the response and the work you do to keep everyone informed.👍

[Hidden in reply to Tall_Allen]

But doesn’t Decipher identify intraductal as a result of PTEN loss? Isn’t that how Epstein identifes IDC? With a stain that shows PTEN loss?

[Tall_Allen in reply to Hidden]

Decipher doesn't identify IDC, that is done by the pathologist. IDC is identified by histology, not genomics. Many prostate cancers show PTEN loss that are not IDC.

[DrRobin]

TA, I am on CFI-400945. The response to the loss of PTEN to it is what brought on the phase 1 trail. The phase 2 trial is 1 week on, 1 week off. Of course I wonder if additive therapy with your ALK inhibitors might be a game changer. Because of protocol of a trial I can’t take them. Also I was randomly selected and don’t know my genome.Maybe we can find a cure.

Thanks!

[Tall_Allen in reply to DrRobin]

What ALK inhibitors are you talking about? I can't recall posting anything about ALK inhibitors for prostate cancer. I think they are only used for lung cancer. CFI-400945 is a PLK4 inhibitor. I agree -stick to the protocol - drug interactions are unpredictable and can be dangerous.

[DrRobin in reply to Tall_Allen]

Sorry I meant AKT. My reply was to that post. As well it was combined with abiraterone which my liver could not break down after 4 months on Keytruda.Hopeless situation ( AST & ALT rocketed) then.

[Tall_Allen in reply to DrRobin]

Yes, they are promising. Capaversatib+docetaxel did extend survival by almost a year in a Phase 2 trial:

pubmed.ncbi.nlm.nih.gov/333...

[DrRobin]

AST & ALT was too high with even reduced dosages of abiraterone. Alk.phosphatase is really high at present: that is why I hope the PLK4 inhibitor helps me. I grab at all straws. Oh I am a retired dentist just trying to navigate through all this.

All your posts have been helpful!

[Keeper70]

hi TA

I had to dig in the archives to find posts about PTEN

My husbands molecular and genetic/somatic did not indicate loss but was expressed as CNA -seq deletion not detected and seq dna tumor, mutation not detected, there was a number also TPM/percentile in cancer type 78/48

Can u tell me what that all means? Thanks in advance for any clarification

[Tall_Allen in reply to Keeper70]

It means he does not have PTEN loss, which is a good thing. PTEN is a tumor-suppressor gene, so its loss allows tumors to replicate.

[Keeper70]

👍Thank you TA for replying on such an important test! We feel so much better knowing he does not have PTEN loss