Three-drug combination prolongs survival: Press Release

[markoch26]

Click on the link below:

massgeneral.org/news/press-...

Published by Massachusetts General Hospital on Feb. 18, 2022.

Thanks.

[Schwah]

Once again it is proven that more treatments earlier are far superior to sequential treatments. Schwah.

[6357axbz in reply to Schwah]

Schwah, I didn’t see where this triplet therapy was given up front, at diagnosis but it seems from other articles I’ve read recently that is a requirement for theses multiple drug therapies, especially the docitaxel.

[Hidden]

Another triplet combo: ADT, Docetaxel chemotherapy plus Zytiga has also proven to extend life in the PEACE 1 trial.

[GP24]

They did not check if ADT+Daroluamide works just as well as ADT+Chemo+Darolutamide. I believe it is likely that you can omit the chemo.

[CAMPSOUPS in reply to GP24]

Emit chemo when fully metastasized ?I think you meant under certain circumstances depending on Gleason, spread, etc. no ?

[GP24 in reply to CAMPSOUPS]

I am not against chemo! However, the triplet therapy is based on the PEACE-1 and Arasens trials which included de-novo metastatic hormone-sensitive patients. So it just applies to de-novo hormone-sensitive patients. Both trials did not test what results the "triplet therapy" without chemo would have. And I assume the added benefit of the chemo component is very small.

Dr. Eleni Efstathiou made a video presentation raising the question: is docetaxel still needed for hormone sensitive metastatic PCa? She expresses doubts that the chemo is beneficial in this situation.

high5oncology.tv/fileadmin/...

[Hidden in reply to GP24]

"Both trials did not test what results the "triplet therapy" without chemo would have."

That's true, but you can compare other trials and see the differences.

For example, CHAARTED showed a 57.6 month median overall survival for ADT plus Docetaxel. LATITUDE showed an median OS for ADT plus Zytiga of 53.3 months. ADT plus Docetaxel plus Zytiga in PEACE 1 showed a 5.7 year median overall survival. That's a significant improvement over any other combination so far.

onclive.com/view/adt-based-...

[GP24 in reply to Hidden]

One should not compare different trials because the cohorts are different. However, it is often done.

I just expressed doubts that chemo is really needed in the "triplet therapy". There are a lot of reports now advertising the triplet therapy. However, Prof. Sator expressed doubts too. practiceupdate.com/content/...

Also, in the Enzamet trial ADT+Xtandi had better results regarding OS than ADT+chemo+Xtandi.

nejm.org/doi/full/10.1056/n...

nejm.org/doi/suppl/10.1056/...

So I still have my doubts.

[GP24 in reply to Hidden]

I had cited Prof. Sator regarding the PEACE-1 trial. He also questions the chemo component in the Arasens trial. He mentions that the STAMPEDE trial showed very similar results for ADT+Abiraterone compared with the Arasens trial with ADT+chemo+Darolutamide.

practiceupdate.com/C/133110...

[Hidden in reply to GP24]

I think LATITUDE VS PEACE 1 is a better "apples to apples" comparison. It's the same drugs with or without chemotherapy.

[reb77 in reply to GP24]

I thought the literature said that Daroluamide was only for NON-METASTASIZED PC. Thoughts?

[GP24 in reply to reb77]

Recently the Arasens trial was published which tested Darolutamide+chemo+ADT in metastatic hormone sensitive patients.

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

[reb77 in reply to GP24]

Thanks. I am on Orgovyx + Zytiga + Predinsone. I'll check with my Oncologist and get his feedback.

[GP24 in reply to reb77]

This trial was positive but the FDA has not approved Darolutamide for this situation yet. Probably the manufacturer has not filed an application for it yet.

[pjoshea13]

If my addled brain is correct, the result can be restated as:

At 3.5 years, 49% of controls (318) had died & 33% of triplet-therapy men (215) had died.

Schwah says "far superior".

I wonder how many other drugs must be added to the trio before most men survive 3.5 years?

-Patrick

[Schwah in reply to pjoshea13]

Ask the 103 men that would have been dead (318-215=103) if it was far superior. It’s an ugly disease and improvements are incremental. But if that were the treatment protocol (vs the placebo) for say 300,000 men, an extra 100,000 men would be alive at 3.5 years. In the stampede and Latitude trials the difference was 40% more alive for those that did the Zytega and ADT bs ADT alone. The point being that many oncologists had been going by the theory that you use one treatment until it failed and then on to the next. The idea being to “save treatments”for the future and not use them up to quickly. Numerous studies now have proven that approach leaves more PC Patients dead sooner. Do you not agree with that?

Schwah

[pjoshea13 in reply to Schwah]

The sequential approach is mathematical nonsense, of course, but I think it goes back to the time when one was on ADT for 18-24 months, with lackluster Taxotere in reserve. No triplet option. Then Casodex happened, of course, but still not a lot of interest in throwing everything at it, with nothing at all left after the inevitable failure.

In a study such as this, results have to be published before all of the men in the study are dead - I understand why. But we don't know how the survival curves look for those who survived the first 3.5 years.

An extra 16% of the cohort made it past 3.5 years - the glass half full (you).

33% of the cohort were dead within 3.5 years - the glass half empty (me).

-Patrick

[btca in reply to pjoshea13]

Reading through all this is disheartening--the prospect of entering this sequence of events and treatment outcomes and the short likely unpleasant journey is something I hope to avoid---one way or another.

[Schwah]

Lol. Interesting points. Think positive my friend.