Combination therapy in metastatic hormone-sensitive prostate cancer: is three a crowd?

[CSHobie]

This is quite new, have you seen this already

This is for Hormone sensitive men.

journals.sagepub.com/doi/10...

[PGDuan]

Thanks for sharing - I missed this article, but for the CSPC crowd here it is a good synthesis of the latest trials and current thinking.

[tango65]

The randomized control trials have shown that in newly diagnosed (de novo) castration sensitive metastatic cancers treated with triple therapy (docetaxel, abiraterone and chemo or ADT, darolutamide and docetaxel) improve survival. The darolutamide trial also included patients with BCR , but 86.1% of the patients in the study were newly diagnosed.

[CarlosBrasil in reply to tango65]

Thanks for the heads up, a subtle difference, but easy to mislead someone not experienced in the subject, like me.

[tango65 in reply to CarlosBrasil]

I made a mistake, the darolutamide trial included patients with BCR.

[Purple-Bike in reply to tango65]

My understanding is that ARASENS showed benefit from adding Darolutamide (vs placebo) to ADT and docetaxel for both de novo mHSPC HR=0.71 and recurrent mHSPC HR=0.61. Slides 17/18 from Medscape "Improving outcome in metastatic hormone sensitive prostate cancer".

[tango65 in reply to Purple-Bike]

You are right, my mistake.

[tango65 in reply to Purple-Bike]

I'll appreciate if you could post the link to your Medscape reference. I could not find it in Medscape.

[Purple-Bike in reply to tango65]

I do not manage to retrieve the slides with a link. If you message your address I will e-mail them.

[Hidden]

Hec NO! Hobie! Three’s company . Knock that pc back to the dark ages …💪😂

[CAMPSOUPS]

As mentioned this is for newly diagnosed metastatic and includes hormone sensitive.I missed it by about a year.

The word was out before completion of the Peace-1 trial but my Dr. wanted to sequence my treatment instead so I had to wait a year after my chemo when PSA and progression started to get on Zytiga.

Now with the Peace-1 trial completed it is SOC to do all 3 at once.

[MateoBeach]

De novo metastatic PC would be HSPC by default, never having been treated, exposed to or evaluated for response to ADT. Moving on to those with BCR or treatment failure of primary surgery or RT to the prostate. They may already have metastasis, at least micro-metastasis even if not yet visible on scans. Hence not diagnosed as M1. How are they different? Could they not also have improved outcomes by adding early Docetaxel to their (SOC) ADT plus AAR drug?

Even as we are learning that early docetaxel otherwise adds very little to long term OS.

Complicated. But perhaps Triplet worthy of exploring in high risk BCR not previously treated with ADT regimens.

As Lulu said: "Hit hard and early" may be superior to saving your ammo.

[d3is4me]

Hi CSHobie Thanks for this post very interesting for me as I was DX De novo metastatic and only having Firmagon and Abiraterone+ Prednisone this is not SOC Australia

[Cooolone]

Sequencing therapies and the timeline of effectiveness is certainly a major question when one becomes metastatic! I don't believe there is any published guideline that clearly provides a thorough description, especially with respect to burning lines that shape future therapy availability.

So, the road ahead is always akin to an early morning fog! In all probability, likely due to the heterogeneous nature of this dastardly disease! My cancer, isn't YOUR cancer...

So yeah, like in any fight, you want to stun early, knock the wind out of your opponent and benefit from not having to fight hard to finish things off! But I'm not sure if physical fighting translates to biomedical, lolz... 😂

Keep on Truckin'

✌️

[Spyder54]

Read it all. Took 30 min. My brain is now exhausted for the morning. A good look at Triplet therapy thru 7 diff Trials. Summary was great. A case could be made that Docetaxel is best for high burden Metastisis. Thanks, Mike

[CSHobie in reply to Spyder54]

Yes, that is what I basically see. The traditional way of thinking that some treatments works better for Castrate resistant disease, is not necessarily true.

[CAMPSOUPS in reply to Spyder54]

Yea I was a mess at diagnosis. High burden mets. Lupron was a good start as I quickly felt better and got my appetite back but the chemo that started a month after lupron really started to mitigate my symptoms albeit mixed with chemo side effects.

[Purple-Bike]

This is radical. In the ARASENS study, triplet therapy Daralutomide vs placebo, in addition to docetaxel + ADT, showed HR = 0.61 for 86 patients with mHSPC who. had "recurrent metastatic disease".

Does anyone know if this likely means new mets identified on scans, or if it could include only PSA progression from undetectable with clean scans?

[Purple-Bike in reply to Purple-Bike]

The data in the study do not show the definition of "recurrent metastatic disease".

As evidence stacks up, we gradually learn that the earlier the better. My bet would be to add daralutamid/Nubeqa when there is some sign of progression, be it consistent rise in PSA from undetectable or consistent rise in bone-ALP, before it gets to new mets being identified.

Daralutamid + ADT, not sure about docetaxel.

[Teacherdude72]

Nubeqa is now approved for this too

[Purple-Bike]

Whereas ARASENS shows a benefit of adding daralutamid to ADT + docetaxel for de novo and recurrent mHSPC, it is also stated that it is not clear whether docetaxel provides a benefit in addition to daralutamid and ADT.

According to the article linked by CSHobie, not refering only to Arasens, "the benefit of docetaxel (for mHSPC) may be mainly confined to patients with high-volume synchronous mHSPC, although this is contentious".

[Spyder54 in reply to Purple-Bike]

Yes, Purple-Bike, it read the Arsens Trial results the same way, unless there is a heavy tumor burden of bone mets and or lymph mets, then Docetaxel did not add much more benefit than ADT + Darolutimide. Lot of toxicity without a lot more benefit.

[Purple-Bike in reply to Spyder54]

Right, Spyder54. I held abiraterone higher but with ARASENS it's tipped over to darolutamide+ADT now seeming to be the most promising treatment for recurrent mHSPC.