Nubeqa monotherapy question

[Steel67]

anyone on Nubeqa monotherapy with their prostate intact? I’ve been on it this year with Mets having resolved. ….my PSA rose from .03 to .150 after I got off of Orgovyx and I continued w just Nubeqa….it has remained there all year, with T at 500. No doctor can tell me what it should be - they just say undetectable is better. CTC count is zero. No disease evident on PSMA and FDG.

I’ve investigated what the action of Nubeqa is on androgen receptors in the body, and on the prostate. Certainly I wish it was undetectable, should I be doing more?

Should the Nubeqa be shutting down all PSA? Would a healthy man on Nubeqa theoretically be at zero?

thank you to any members with relevant ideas, opinions or experience !

[Justfor_]

The importance lies in the trend, not that of any particular value. You have reached equilibrium, that is any new PSA producing cells are offset by the killing or falling into dormancy of a comparable preexisting population. This milder evolutionary stressful mechanism, IMO will prolong your hormon sensitive period.

[Steel67 in reply to Justfor_]

appreciate the response!

[Tall_Allen]

Anti-androgen monotherapy with enzalutamide has been proven to be inferior to ADT+enzalutamide in the EMBARK trial.

•Relative to the control group, the incidence of distant metastases was reduced by 58% by combination therapy, and by 47% by enza monotherapy.

•Overall survival results are not yet mature, but so far mortality has been reduced by 41% by combination therapy, and by 23% by enza monotherapy

•Time to PSA progression (castration resistance) was increased by 93% by combination therapy, and by 67% by enza monotherapy.

•Time to chemotherapy was increased by 64% by combination therapy, and by 46% by enza monotherapy.

prostatecancer.news/2023/05...

I can't think of any reason why darolutamide should be different.

[Steel67 in reply to Tall_Allen]

Great info thank you

[IKNY in reply to Tall_Allen]

Thanks T_A, heartening information!

All the best

IK

[Pianodude]

I started on Nubeqa mono therapy in August after being on Orgovyx and Nubeqa for a couple years. A PSMA PET in August showed that my cancer and bone metastasis was basically undetectable. My PSA was 0.2 in October. My testosterone is 14. I hope that it comes back a bit more to mitigate the side effects from ADT a bit. We are going to closely monitor labs and do scans every 6 months.

[Shellhale]

So to answer this question have you had prior treatments? Chemo or radiation prior to monotherapy Nubeqa? That really makes a difference. Embark trial showed these men had prior treatments before monotherapy Xtandi. My husband dx 9/2023 Stage 4, was on monotherapy Xtandi for 10 months with gleason 9. Only 1 round of chemo that was discontinued. Also did other alternative treatments and off label drugs and supplements along with low glycemic diet. His PSA started rising after 5 months from nadir 1.0 and doubled within 3 months. ADT Orgovyx then started for 3 weeks and discontinued. Psa went from 3.1 to 0.6. Then started radiation to prostate only since prior lymph node mets showed resolved (12 mets to retroperitoneal) 20 sessions of radiation ended 8/16/24. PSA rose again prior to radiation to 1.15 and now PSA is 0.46 and he is on monotherapy Nubeqa. Interested in other similar experiences as well.

[Steel67 in reply to Shellhale]

yes prior treatments: Started with Orgovyx, 3 rounds Lutetium, focal cryo with 3 immunotherapy injected into prostate , and finally radiation to one remaining met. Now on Nubeqa mono. Considering Provenge, then open to going back on Orgovyx.

[Samrecan in reply to Shellhale]

Could you please share the off-label drugs and dosage he used.

[Shellhale in reply to Samrecan]

So the off label drug protocol we use is based on Ferroptosis causing lipid peroxidation and inhibiting other metabolic pathways. Metformin 500 mg BID

Pitavastatin 2mg QD

Celecoxib 100 mg BID

Ivermectin 55 mg once a month

Mebendazole 225 mg QD 3x week

Naltrexone 3mg 3 days on and 4 days off QD

Intraconzole 100mg QD 1 week on and 1 week of

Tadalafil 5mg QD

Doxycycline when able to tolerate dont know dosage right now.

He also takes a bunch of nutraceuticals.

[Shellhale in reply to Shellhale]

Update PSA is now 0.27. Testosterone went down 274 probably from being off diet for almost 2 weeks on vacation. Typically T fluctuates 500-990. Also switched from Xtandi to Nubeqa because of less side effect profile. Nubeqa doesn't cross blood brain barrier.

[jazj in reply to Shellhale]

Are you sure about that less side effect profile? I would venture to guess the majority of people here did Xtandi monotherapy, with a minority Nubeqa so there's not as much anecdotal data here regarding Nubeqa compared to Xtandi. And probably within those groups many were also doing ADT. The DEAR study showed Nubeqa monotherapy was more effective and with less side effects than Xtandi. This is for monotherapy (not taking anything else). Each individual can respond differently so the saying "Your Mileage May Vary" comes into play. I'm pretty sure both cross blood brain barrier as one of the side effects of Xtandi is brain fog.

targetedonc.com/view/darolu...

"Treatment discontinuation or progression to metastatic disease occurred in 37% of patients (n = 340) treated with darolutamide compared with 51% (n = 187) of patients treated with enzalutamide and 51% (n = 62) of those treated with apalutamide. The median time to discontinuation or progress to metastatic disease was not reached in the darolutamide group (95% CI, 30.1-NA). In contrast, these events occurred at a median of 23.1 months (95% CI, 18.2-26.4) in the enzalutamide group and 20.5 months (95% CI, 12.3-27.2) in the apalutamide group."

"In particular, adverse events occurred in 9.7% of patients in the darolutamide cohort, 14.4% in the enzalutamide cohort and 15.7% in the apalutamide cohort. Progression to metastatic disease or death was observed in 8.8% of patients treated with darolutamide, 12% in those treated with enzalutamide and 13.2% in patients treated with apalutamide."

[Shellhale in reply to jazj]

Thank you sharing that data. I was told by husbands genitourinary oncologist that Nubeqa has a less side effect profile. My husband was having dizziness spells every day throughout the day and MO suggested that he switch from Xtandi to Nubeqa. After a few weeks the dizziness has subsided. So for him it has proven to work with that known side effect from Xtandi.

[jazj in reply to Shellhale]

Your husband's Oncologists advice is in alignment with the clinical study results. Nubequa was first approved July 2019 and Xtandi August 2012. This would explain why there is much more anecdotal reports regarding Xtandi. And it isn't surprising a 7-year newer drug apparently works modestly better with a modestly better side effect profile (on average.)

[Shellhale in reply to jazj]

Also his testosterone went from 543 to 274 when he switched from Xtandi to Nubeqa. I don't know for sure if it's related or not. We will have to do labs again in another month to compare. Also his testosterone was drawn in the afternoon verses in the morning when the prior lab was taken. Testosterone levels tend to be higher in the morning from what I have heard. Is that correct?

[jazj in reply to Shellhale]

You have gone past my current personal body of knowledge. So hopefully someone else can chime in. My lay understanding of these ARI drugs though is that they block the testosterone from the cell receptors but don't work like traditional ADT drugs that actually are designed to block the production of testosterone (to < 50.) Your husband is in a very different stage than me though so I really have no opinion on his treatment strategy. I'll say one thing, even though I'm not technically and Advanced PCa patient, after participating in many forums, this is the only place I determined was worth spending all the time on to get other patient input. This forum in my opinion has the smartest people on it. You are wise to be here.

[Shellhale in reply to jazj]

That's why I am here. I actually work in the medical field as a RRT. I find this site to be more analytical, researched and evidence based. I do use ancedotal as part of my research also. Sometimes you just learn more from the patients experiences. As I tell my patients this as well. ARI block uptake to the cell so this prevents testosterone from stimulating cancer cell growth regardless of the testosterone levels in the body. Just thought it was interesting that his testosterone levels were lower but again it may just be the time of day that the blood was drawn.

[Shellhale in reply to Samrecan]

I realized I forgot to include Metformin 500 mg BID

[Samrecan in reply to Shellhale]

Thanks for the update

[Shellhale]

What is your gleason score? Seems that you've kept your PCa under control. Do you know what your testosterone levels are? Since you still have your prostate i would use your psa nadir and if it goes up by 2 ng above that then would get PSMA scan. That is what we are doing with my husband. He doesn't tolerate ADT and is not open to it at all. So really hoping he can continue monotherapy nubeqa and if psa rises then psma scan with SBRT to radiate any hot spots is the back up plan. I also know some men who use orgovyx intermittently. I know there is new promising drugs coming in 2025 so that is very encouraging.

[Steel67 in reply to Shellhale]

Gleason 9 T is 500- thanks for your response

[Shellhale]

His T is around the same. Everything will be good. Wishing you all the best and continued success.

[j-o-h-n in reply to Shellhale]

Hello Shellhale,

It may be a good idea to cut from you posts above and paste them in your dear husbands bio. It will be helpful for him/you and for us too. Thank you!!!

Good Luck, Good Health and Good Humor.

j-o-h-n

[Shellhale in reply to j-o-h-n]

Thanks John I will do that. God Bless.

[dhccpa]

Excellent question. Have you had radiation or chemo?

[IVA65]

I'm on both and PSA went from 1.0 to 0.12 in 5 weeks. I'm very new to all this. Getting docataxel in 10 days, then every 3 weeks for 4 months. I'm sorry I cannot give you any more insight, but I did have to emphatically push for 3rd component of therapy to get to this point. I've also requested bone preserving drug too.