Adding PARP inhibitor (Olaparib) to the Standard Therapy (Zytiga/ADT/Prenosone)

[snoraste]

I had an interesting and unexpected conversation with my "second opinion" MO. I went to see him regarding adding Metformin to my list of medications (He's a well known expert - more on Metformin later), but the focus of the conversation turned into adding Olaparib to my existing treatment regime of Zytiga/ADT/Prednisone, because of my BRCA2 mutation.

He basically shared his intuition and gut feeling with me - no phase III certainty. He suggested that adding Olaparib BEFORE cancer cells can form large colonies and become castrate resistant should improve outcomes. He pointed out - correctly - that if past decade of cancer research has shown us anything is to act EARLY and AGGRESSIVELY (as tolerated).

My initial reactions were three folds: First, why not stay the course and wait for more effective PARP formulation (e.g. nano formulation) down the road. Second, What if I develop early resistance against PARP because of the early introduction. Third, the side effects. He admitted they are real risks, but pointed out that they had the same concerns with adding docetaxel and abiraterone in STAMPEDE and LATITUDE trials which were proven wrong. PARP inhibitors are also "generally" well tolerated.

I'd like to hear thoughts from the members here, especially those who have been on PARP inhibitors.

As for Metformin, he said he just released a paper on his latest "Telemedicine-Enabled" study (JCO publication). His conclusion:

"Metformin was generally well tolerated but associated with modest anticancer activity".

In person he was a lot more upbeat about its use and effects and suggested I add it to my intake.

[snoraste]

Thanks Nalakrats. I looked at the nano formulation on Dana Farber's web site - but cannot find the research. Do you happen to have a link to it?

[pjoshea13 in reply to snoraste]

ncbi.nlm.nih.gov/pubmed/285...

[snoraste in reply to pjoshea13]

thanks Patrick -

[vandy69]

Good Morning snoraste,

Please see my bio for treatment history. I took Lynparza for about 1 year after found ATM defect.

Very expensive, so check insurance.

No real side effects.

Hard to determine effectiveness, but I am still here!

Best wishes. Never Give In.

Mark, Atlanta

[sammamish in reply to vandy69]

Hi Vandy, I am proffering a somewhat delayed response as I just now stumbled across your post. Was your ATM defect tumor based or germ line? If germ line, did you avoid radiation therapy? Struggling with the ATM question as it relates to radiation.

[vandy69 in reply to sammamish]

ATM defect was picked up by a Guardant360 liquid biopsy.

Lynparza worked for about 9 months but I still had proton beam radiation and later chemo.

Best wishes. Never Give In.

Mark, Atlanta

[sammamish in reply to vandy69]

So from what I've read, the 360 can distinguish between germ line and tumor specific mutations. Did they inform you which it was?

[vandy69 in reply to sammamish]

Not that I recall. Sorry.

Mark

[snoraste]

Just to give an update on this topic.

I spoke to 5 professionals from 5 different cancer institution: MSK, Mount Sinai, a private Biotech company specializing in prostate, Weill cornell, and DanaFarber.

On the 5, only Mount Sinai was strongly in favor of the addition. The private biofirm was undecided, and the other three, all suggested that it makes sense to hold off. The reasons:

- The effect of PARP, as an stand alone addition to abirateron seems to be limited.

- There are studies in MSK to combine PARP with an immunotherapy agent (I think PD-1 or PDL-1) that seems promising. Dana Farber doing their own combinations of PARP and another enzyme that he said looked promising as well. Dana Farber MO suggested they are a year or two away. Both argued that the early use of PARP may cause early resistance, which can hinder its effect once the new combination treatment is approved. Why take the risk, knowing something better is coming soon?

I asked Dana Farber about the nano formulation or Olaprib, he said the trial/research is outside of the prostate cancer center, and he had no idea if/when there will be a trial for PCa patients.

Dana Farber was actually IN FAVOR of local therapies (they prefer radiation) for advanced PCa. They have a trial going on now with MSK. He also was open to adding Metformin, and - surprising to me - Aspirin and Coffee!

I just changed my MO at MSK and going with a more "aggressive" MO over there. I'll keep you posted about his thoughts when I meet him in a month.