azd5305 PARP inhibitor

[Maxone73]

I had the chance to ask a doctor about this, the doctor is the chief of this trial in one center of excellence here.

I went there to know the options for when I will become CR of course. To be honest, I discovered that in Italy at the moment no PARP inhibitor is allowed for ATM mutations, only BRCA and few others. I was a bit disappointed even if he said he thinks that since I had a great response to the first line triplet therapies, many more drugs will be available when I will need them. But apart from this bout me, I have asked how AZD-5305 is behaving during the trial, and the answer is that it is going very well (and in the next future a study with ATM mutated patients will start!).

So if you need a second generation PARP inhibitor, much safer than the first generation ones (more targeted), keep an eye on the AZD5305 (saruparib) trial!

[Tall_Allen]

Coincidentally, I was just discussing this trial, PETRANHA, with an MO this week with a patient who has an ATM mutation (but no BRCA mutations). Unfortunately, the trial excludes all men that have already had one ARPi (which would be almost all men with mHSPC in the US.)

clinicaltrials.gov/study/NC...

However, Astra Zeneca is also testing another specific PARP1 inhibitor, AZD9574, in their CERTIS1 trial. It even penetrates the blood-brain barrier.

clinicaltrials.gov/study/NC...

Module 5 seems to include patients who have already tried an ARPi.

The nice thing about these second generation PARP1 inhibitors is they don't seem to have the blood and alimentary toxicity of the first generation less-specific PARP inhibitors (i.e., olaparib, niraparib, rucaparib, and talazoparib) and they may work against HRR mutations other than BRCA (like ATM, ATM, ATR, CHK1, CHK2, DSS1, RPA1, NBSI, FANCD2, FANCA, CDK12, PALB2, BRIP1, RAD51B, RAD51C, RAD51D, and RAD54).

I was also influenced to hold off by this small retrospective study that suggests that the patient might do better with docetaxel first:

onlinelibrary.wiley.com/doi...

[Maxone73 in reply to Tall_Allen]

thats what he told me, they are starting soon the second part of the trial, that includes ATM but also people with no mutations, but it's for first line, so the fact that I am using daro is already ruling me out, even if there is always space for compassionate use...I hope his optimistic opinion that by when I might need it all the trials will already be at full speed also for people who already had docetaxel will become reality

by now the only info I got because he is a friend of a friend (we talked 90% of the time about research instead of my own condition) is that for now saruparib is working really really well

[tarzantass in reply to Tall_Allen]

Hi Allen,

I just to want to know whether a person like me without any DNA (BRCA 1 and 2) mutations, can still take olaparib. If yes, is it effective. Thanks.

[Maxone73 in reply to tarzantass]

they are being tested also on people with no BRCA mutation, they help but they are "not worth it" from what many researchers say

nejm.org/doi/full/10.1056/N...

[Tall_Allen in reply to tarzantass]

No. It has been tested and found to be ineffective and not FDA-approved in men without BRCA mutations.:

prostatecancer.news/2019/10...

[j-o-h-n]

"To be honest" Uh Uh Uh

Good Luck, Good Health and Good Humor.

j-o-h-n