Abiraterone/prednisone plus olaparib extends time to progression in BRCA/ATM mutated prostate cancer.

[Maxone73]

I have already talked about this data, but it's worth repeating...plus when I see dr Hussain I always smile!

“Our data showed that the combination therapy resulted in more than two-fold increase in the median time to disease progression compared to single-agents or sequentially following progression,” Hussain said.

We are talking about a median time to progression of about 39 months (22 months to not reached)...amazing second line combo. I would like to see the data stratified between BRCA and ATM. At first glance, the sample appears to be unbalanced in favor of BRCA2.

news.feinberg.northwestern....

aacrjournals.org/clincancer...

NOTE: there is a more selective PARP inhibitor now, Saruparib, which is less toxic as it can target PARP1 only, almost without affecting PARP2. Of course there should be a study using the same plus Saruparib to be sure the synergistic effect is still there, but keep that in mind in case you were thinking about PARPi.

[Maxone73]

I try my best fratello! 😀

[Hidden]

I'm on 3 Parp groups for Ovarian cancer. The shit is bad news

[Ian99]

Ciao Max. Thanks for posting about this complex area. I am 3+ months on olaparib, finding it v toxic. Awaiting next blood counts and scan compares.

From what I read.. in contrast to parp1, parp2 binds less efficiently to DNA single-strand breaks (SSB) but instead recognizes gaps and flap structures. So parp2 is less toxic. But I find disappointing that it will still operate against both cancerous and non-cancerous cells as they all contain the brca2 (my case) gene. That said, I’ll take away that AZ are looking to make it less toxic, which is good. Buona giornata.

[Maxone73 in reply to Ian99]

Interesting! I will have to investigate further but saruparib rationale was that it’s less toxic because it binds to PARP1 500 times more than it binds to PARP 2. In fact it’s marketed as parp1 inhibitor specifically.

[Jazzman2023]

Thanks !! Have there been similar parp-related drugs/studies that benefit BRCA2 like sauraparib benefits BRCA1 ?