[Rick Davis]

This one is a bit beyond my paygrade, @highanxiety, but I hope our Brains Trust will respond on the issue of QC for generic drugs.
O&U

[Rick Davis]

ATM is a tricky HRR mutation from what I know @notsdr. It was what pulled us into this in the first place back in 2020 because it was considered actionable in Jake’s GRHS FMI report. Len will correct me if I am mistaken, but ATM had some response to PARP’s in the PROfound trial but not enough to make it significant.

W.r.t. to the BRCA question in PROpel, all participants were tested for germline. I addition I think most were tested somatically but many on old tissue – for example from a former RP. There was a complaint from AZ (inc Shore and George) that testing bone was unreliable due to the maceration process. And that many docs did not order somatic tests. No one, including the FDA, suggested ordering both liquid and solid tests, that you can do. Dr. E did that for Steve Saft z”l. There are some quirks but it can be done.
I believe AZ ran numbers for all the HRR variants. I recall it being said there were not enough of some of the lesser variants to be significant. I’d have to go through again to find more… but feel free to write to Neal Shore and ask him about ATM in PROpel.
Worse than the poor rPFS for all comers, the OS was 1.07 with olaparib and abi. That says, you are MORE likely to live shorter than the control arm.
You ask:
Who should the patient believe and rely on: Pfizer, which has the overwhelming approval of the FDA, or the Committee representative?
Did you just switch gears to speak about Talapro2 and the Talzenna + Xtandi approval? It’s a good question that I have pondered. Why have they approved talazoparib + enz for all HRR mutations and not just BRCA mutations?
Well, the non-BRCA HRR Hazard Ratio was 0.72. What I don’t know is the split between HRR mutations, but I feel sure Pfizer/the researchers do. I can’t find it released publicly but Dr. Fizazi mentions it in his clip below.
I was hoping we would get into that in the webinar but Shore split early although not before clearly stating that anyone who wants a PARP should be allowed to try it. So we know where he stands.There is likely some synergy from the two drugs. But there is also significant toxicity.
Listen to Dr. Fizazi https://www.urologytimes.com/view/dr-fizazi-on-pivotal-talapro-2-trial-of-talazoparib-enzalutamide-in-hrr-gene-mutated-mcrpc. He states that CDK12 does well, while ATM and CHK2 do not! He also suggests the FDA may return to narrow its approval.

[Rick Davis]

Hello Tom … venlafaxine (Effexor) can be prescribed to prevent hot flashes. It is primarily used as an anti-depressant (SNRI). For some men, including one in the meeting on Monday, it may be an antidote for hot flashes.
O&U

[Rick Davis]

Hello Tom … venlafaxine (Effexor) can be prescribed to prevent hot flashes. It is primarily used as an anti-depressant (SNRI). For some men, including one in the meeting on Monday, it may be an antidote for hot flashes.
O&U

[Rick Davis]

@notsdr ….. I don’t think it is approved for mHSPC alone unless accompanying chemo. Len can correct me. So it has to be offered off-label and that makes life complicated.

[Rick Davis]

Tx for getting this rollin’, Mr. J!
O&U

[Rick Davis]

I’d agree with Steve that the absolute numbers look low based on anecdotal experience.
Ido think the factors Len outlines may explain that

[Rick Davis]

I’d agree with Steve that the absolute numbers look low based on anecdotal experience.
Ido think the factors Len outlines may explain that

[Rick Davis]

I noticed the cognitive numbers for enz and apa too and questioned them! I haven’t had the time to check them out – my gut tells me there is more to it. There has to be more…

• This reply was modified 1 year, 5 months ago by Rick Davis.

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