This is a phase 3, large number international trial of the combination of abiraterone (abi + prednisone) with a newer PARP inhibitor (PARP-I), Niraparib (nira). It is run by Janssen/Johnson & Johnson who hold the patent for abi. They are no doubt hoping to extend the patent and make a combined abi/nira a standard of care (SOC) for men with DNA repair mutations. In terms of effect on PARPs, nira is a lot more powerful than olarparib but not as powerful as another recently developed PARP-I, talazoparib which is about 100 times as powerful as olarparib but has had few human trials and is rumoured to have some fearsome side effects. Nira is already approved and in use in the US for ovarian and breast cancer. They are looking at people with DNA repair mutations (DRM) such as BRCA 1 & 2, CDK 12, ATM. BRCA occurs in a small but not insignificant portion of men with PCa
There are 3 arms to this trial. All concern men with failed ADT who are about to use, or have been for less than 3 months, abiraterone. They can have prior radiation. I’m not sure about chemo. The first arm does not use any genetic restriction and that is determined at the end. So its basically a sample of ordinary everyday advanced PCa men. They are split in 2. One half just gets abi. The other half get abi+nira (all +prednisone). It’s blind so no one knows which they have. In the other 2 arms everyone has DRMs, mostly BRCA. The second arm is the same as the first except that all subjects have a relevant DRM. In the third arm all DRM subjects get abi+nira.
That is the arm that I am in by a combination of luck and having BRCA 2 (not so lucky). It is nearing 4 months and during that time an amazing array of blood tests and scans. Mucho resources. I am well examined. So far nothing worrying has come up and bloods are generally OK. PSA has gone from 25 at the start to 15 now. Scans show a diminution of nodal mets but no change in bone mets.
Apart from one, all side effects are mild and really not that different to ADT/antiandrogens. Abi has a well known side effect profile.
The bad one is the mother of all constipations. Nothing taken according to instructions had the slightest effect, even when taken together, even when doubled.
Now a word about laxatives. Like many men my age, I have diverticulitis. It is a weakening of bowel walls so that pockets extend outwards. It is controllable, but becomes critical when a pocket bursts. There are 2 rules. 1. Never get constipation and 2. Never strain. OOPS. There are 2 types of laxative. The first and by far the most common are stimulating agents that cause the bowel muscles to twitch and send the package down the line. The second are stool softening agents that send water into the bowel by osmotic pressure. Some laxatives work by a combination of these 2. Obviously I should use the 2nd kind predominantly. (but a small amount of the other helps) Eventually the mother of all constipations yielded to the mother of all osmotic laxatives, Epsom Salts (magnesium sulphate). This is the nuclear option because you need a precise personal dose. Edge above that and it’s not pretty. And it can vary from day to day. Very unpredictable but always effective. I have since restored a slight normalcy using combinations of various osmotic laxatives and a small amount of stimulus laxative a few times a day. My consumption of laxatives is 5-10 times any sane dose. It is more than abuse but that is what it takes. However my bloods are so far OK, especially potassium which is also of vital interest to the trial.
I will post occasionaly as time effluxes. Interesting experience.
Actinium/Keytruda/Xtandi trial update after 24 weeks.
Addition of Metformin after Progression on Abiraterone.
Prostectomy trial or not?
