Darolutamide failing after 2 years. Any success if I switch to Xandi or Zytiga or do I need to move to Pluvicto.

[Longterm101]

Dx 2018. PSA 16.

Been on Orgovyx.

Started Second line (Darolutamide) two years ago when PSA started to rise.

PSA rose over the last 5 months from 0.021 (August) to 0.48

I had a few bone mets and several lymph nodes when dx.

Trying to find other treatments since I'm running out of Standard of Care.

Thx for helping!

I'm only 59

[MoonRocket]

I would imagine chemo is next or maybe one of the Lu177 treatments?I assume the genetic testing you had showed nothing actionable. Is this correct?

[Longterm101]

Correct had genetic testing done and came back with no mutations

I really don’t want to go thru chemo. Never seems to last long (remission) and feel like sh&&$ during it

Looking to extend my runway

Thx

[Ahk1 in reply to Longterm101]

Have you tired Erleada? I am not sure it will be effective or not but just thought of it.

[MoonRocket in reply to Longterm101]

I think you're a wee bit older than me (57), you might be able to get by with 3 cycles of chemo and then try the nubeqa again. Could be a compromise that extends the runway. Your PSA is still low..if you have any mets that are treatment worthy, you could add that also.

[Longterm101 in reply to MoonRocket]

thanks. Lot of think about

[Longterm101]

no but i'm already on another form of hormone blocker

[Tall_Allen]

When your PSA reaches over 2.0, or the PSADT is less than 9 months (on 3 PSA tests over 0.1) you can switch to docetaxel+enzalutamide as in the PRESIDE trial:

prostatecancer.news/2022/10...

[Longterm101 in reply to Tall_Allen]

Thx TA. Why not just go straight to Pluvicto

[Tall_Allen in reply to Longterm101]

Because Pluvicto is only approved after chemo. A small trial showed that there is no advantage in going straight to Pluvicto:

prostatecancer.news/2023/09...

And PRESIDE shows that combining Xtandi and Taxotere is better than Taxotere alone. So the combination may be better than Pluvicto.

[Longterm101 in reply to Tall_Allen]

Thank u

[Joeym1040 in reply to Tall_Allen]

TA - I took Daralutamide for about 6 months before it failed. I then went into the SPLASH trial which helped for about about 6 months and now PSA is rising so i am probably headed for Taxotere, Will Xtandi be provided even though Nubequa failed?

[Tall_Allen in reply to Joeym1040]

It will not be automatically provided, if that is what you're asking. Discuss with your oncologist.

[Joeym1040 in reply to Tall_Allen]

I didcask once for it and he said no. I'll ask again if it makes a difference if we combine it with Taxatere. Thanks TA

[Tall_Allen in reply to Joeym1040]

I suggest you email him the following, with a note that you'd like to discuss it:

thelancet.com/journals/lano...

[Joeym1040 in reply to Tall_Allen]

thanks again as always. You are probably the best source of information for all us warriors out here trying our best to figure out what is going on.

Thanks again for your knowledge and your patience.

God Bless you and have the Very Best 2024 possible.

Joe

[garyjp9 in reply to Tall_Allen]

What about the PSMA fore trial? Wasn't that about giving Pluvicto before treatment with a taxane?

[Tall_Allen in reply to garyjp9]

No. PSMAfore compared Pluvicto to a second second-line hormonal (after failing one), and showed no survival advantage. (Both groups were taxane-naive.)

[garyjp9 in reply to Tall_Allen]

Thank you

[TwilightZone]

Dalolutamide (generic) and NUBEQA (brand) are the same med in the USA.

[Ramp7]

Have you looked into BAT? Most MO would probably not assist. I met with Sam Denmeade at Johns Hopkins a year ago. He said I would be a good candidate for it. I indeed turned out to be a responded. With that news, my local MO is now assisting me. I use "Propionate" purchased over seas. Denmeade uses Cyponanate which has a much longer half life. Here is a brief vd. urotoday.com/video-lectures...

[Longterm101]

I think my plan is Lu177 and then move to BAT

Similar to what u did.

How long to LU hold ur psa down? Where were ur Mets prior to Lu at Dana faber

[Sisto]

You might also consider Provenge. I had it approximately five years ago and felt I got lots of bang for the buck, SE-wise. It was easily tolerated. Good luck with your treatment, whatever you decide!

[lokibear0803]

if you’d consider changing from darolutamide to some other ARI, you can alternately consider Lu177. PSMAfore has recent results showing this is more effective than switching ARIs for patients like you that are chemo-naive:

urotoday.com/conference-hig...

[Proflac in reply to lokibear0803]

This seems contradictory to TAs analysis of PSMAfore (above).? Can someone interpret? Is it that this trial showed difference to radiographic progression but no or little difference to OS? Is that not a gain worth having That's a genuine question btw. There is a lot of hope and faith in Pluvicto for obvious reasons. But I am thinking that we need to keep the reality of the current trial data in mind especially when one has to pay out of pocket (in UK) and other tried and tested options are still available. I would like to read about trial endpoints, what they might mean for how pts feel and what we should be using to judge trial outcomes. Thanks.

[lokibear0803 in reply to Proflac]

Hi Proflac - I’m just summarizing my read of the article. You might read the interview, if you haven’t yet, and see if I’m paraphrasing badly. Here are Sartor’s key takeaways:

177Lu-PSMA-617 prolonged rPFS vs ARPI change in taxane-naive patients with PSMA+ mCRPC

Secondary and exploratory endpoints, including PSA response, objective response rate, time to symptomatic skeletal events, and time to worsening in health related quality of life and pain, also favored 177Lu-PSMA-617

The prespecified crossover-adjusted OS trended favorably for 177Lu-PSMA-617, given that the 84.2% crossover rate may have confounded the intention to treat analysis; OS data collection is ongoing

However, for those who crossed over from ARPI to Lu-177: …there was a trend favoring 177Lu-PSMA-617, but no statistical difference in OS between the groups.

So my interpretation is a patient choosing RLT (i.e. Lu177) over a change of ARPI is better off wrt RPFS, ORR, etc. That was, it seemed to me, a useful answer to the OP…

…but so far there is no clear OS advantage (there is, so far, only a trend). So, to answer what I think is your question: for me - yes, better RFPS/etc are useful goals wrt quality of life, even if this may not mean a prolonged OS. Seems like a personal decision.

But, I wasn’t inferring anything about RLT vs chemo; as I understand it, this trial did not make that comparison, it simply selected a population that was taxane-naive.

HTH.

[Longterm101]

thank u for the info !!