Confused about doublet therapy vs triplet therapy for prostate cancer

[Jdhanoa]

Hi all,

My dad was recently diagnosed with stage 4 advanced metastatic cancer that’s spread to his bones, Gleason 4+5. He was in good health prior to this and came as a shock to us all, he’s 65. We are now trying to figure out the best treatment plan for him. His MO treatment plan is ADT (zoladex) + AR pathway inhibitor. However, i've been doing a lot of research and many people recommended a triple therapy approach to include chemo early on. However, the clinical trial articles i've read regarding triple therapy, they don't compare ADT + AR verse (doublet) ADT + AR + chemo (triplet), they only compared ADT + Chemo verse ADT + AR + chemo. Therefore, I am confused as to what the best treatment would be because is the benefit only from the AR which he is already going to be taking?

Thank you

[Tall_Allen]

That's true that the clinical trials comparing triplet to doublet compared it to ADT+docetaxel. All you can do to get a sense of the benefit vs ADT+ARSi is look at what each does individually. The triplet seems to add about a year to survival vs the doublet with ARSi.

Overall Survival in separate trials

[tango65]

The Stampede results about long term survival of ADT plus abiraterone indicates that this combination has a median overall survival of 6.6 years (79 months) which is longer than the triple therapy so far.

urotoday.com/conference-hig...

ncbi.nlm.nih.gov/pmc/articl...

" Median survival was 46 months (IQR 25, 92) in the SOC-alone group and 79 months (IQR 33, not reached) in the SOC + AAP group;"

[MateoBeach]

Since he is metastatic at diagnosis (de novo) and healthy enough to likely tolerate chemo well, then consider that chemo may provide the most benefit if used right away when starting the others. Because they will strongly suppress PC growth, probably for quite a very long time. Chemo only kills actively dividing cells. So it may (theoretically) provide more cancer-killing benefit up front Rather than reserving it for a later stage. Also, having docetaxel chemo makes him eligible for Nubeqa (darolutamide) coverage, a very good option to abiraterone +p if he has any problem with that. Though I agree abiraterone is an excellent first choice as an advanced hormonal.

Decision about the chemo now is difficult given that it certainly is no fun. Some find it quite tolerable and others have great difficulty from it, especially if peripheral neuropathy develops. We each have to make our own decisions of course. I chose early chemo because I didn’t want to leave any treatment “on the table”. Not sure I would do the same again as it was very hard for me on my body and brain. But that was 15 years ago and I am so happy to be alive, active and happy. Best wishes for you both. Paul

[Seasid]

I started Firmagon injections and 6 weeks later when I was deeply castrated I started early chemotherapy 6 cycles of Docetaxel 75mg/m2 every 3 weeks.

Now 5 years later I don't have on the psma pet scan visible metastasis.

I radiated recently my prostate with SBRT MRI guided Linac, Electa Unity Swedish machine here in Sydney.

My latest PSA was 0.37.

My prostate had SUV Max of 14 indicating CRPC and my PSA was 1.4 before starting irradiation of the prostate. The margins are 1mm on the MRI Linac and I don't have side effects 5 months after starting irradiation.

I suggest you start early chemotherapy and stop if you experience any side effects. I developed peripheral neurophaty grade 1. Now I am fine.

Don't miss the chance for early chemotherapy now. It can be a life saver.

[Seasid in reply to Seasid]

My latest PSA was 0.23

6 months after RT (sbrt) 38 Gy in 5 fraction. 5 years after starting ADT. I was diagnosed in April 2018 and now is 27th of May 2023.

[Jdhanoa in reply to Seasid]

thank you for the update Seasid, glad to see your PSA down

[Seasid in reply to Jdhanoa]

The CEO of the Merck company said that 1 out of 3 prostate cancer patients will developed a metastasis during a course if his illness and 70% of the metastatic prostate cancer patients died inside 5 years.

That is all good information but we don't know their treatment. Do we have a global statistic which would show when people with metastatic prostate cancer die?II would be interested in a statistics from a reputable health care system like NHS? Do we have one? All these statistics are from a clinical trials with selected patients. OK, they are randomly assigned to a group but as a whole they are from a selected patients group. They are selected probably by people (doctors) whose best interest is that the drug is approved. Actually that is the main interest. It does not mean that it was in the best interest of the participants to get into that clinical trial or that their life are extended. My first oncologist professor Richard Epstein said that some people live long on ADT alone and a manager of the chemotherapy section of my hospital also said that some people simply live long on ADT alone. I was wondering why would it be good for me to join the PROPEL clinical trial if I don't have a BRACI mutation? Why would it be good for me to take OLAPARIB?

Whatever our treatment decision is it will influence our future.

Again, do we have a real work statistics from NHS for example how long people live on certain treatment and how much is that real world statistics is different from the statistics from a selected participants from a clinical trials?