Xtandi (enzalutamide) +ADT slows metastases in recurrent men

[Tall_Allen]

We recently saw that ADT+Erleada (apalutamide) slows progression compared to ADT alone.

prostatecancer.news/2022/09...

Now we have proof that ADT+Xtandi (enzalutamide) slows the appearance of metastases and delays castration resistance in recurrent men with rapid PSA doubling times.

prostatecancer.news/2023/05...

Early treatment with either may allow extended ADT vacations.

prostatecancer.news/2023/04... (Setting 3)

In these trials (PRESTO and EMBARK), metastases were detected (for exclusion) with conventional imaging. Now, with PSMA PET scans, many of the patients in those trials would be detectably metastatic, so the results are not surprising. Xtandi and Erleada are known to be beneficial among men who are metastatic and hormone sensitive (mHSPC) and are FDA-approved for that indication:

prostatecancer.news/2019/05...

[cesanon]

Thanks

[Medline]

A central assumption in pharmacology is that structurally similar compounds have similar cellular responses. Apalutamide, Enzalutamide and Proxalutamide are similar in chemical formula and belong to the class of organic compounds known as phenyl-imidazolidines.

[Survivor86]

Many thanks. Are you aware of any ongoing RCT’s to determine whether darolutamide (Nubeqa) + ADT produces comparable outcomes as enzalutamide (Xtandi) +ADT without some of the SE’s of enzalutamide?

[Tall_Allen in reply to Survivor86]

There is a clinical trial (ARANOTE) for darolutamide. It is closed to recruitment now. But I'm not sure that it spares many side effects (unless one is in the small group that gets seizures)- they've never been compared.

[treedown in reply to Survivor86]

I tried to get on Nubeqa and Lupron but was refused and approved for Xtandi and Lupron. The content of this post may be why. The side effects on Xtandi seem more than Zytiga. If my side effects continue I may be able to get a swit h to Nubega approved. In one paper I read Erleada (apalutamide) does not list gynocomestia as a side effect. It also has RCTs for approval of earlier use. May be able to pick your poison for mCSPC in the future.

[TEBozo]

" It is likely that even intermittent use will be advantageous. Recurrent men with rapid PSADT after salvage radiation should consider a short-term intervention with one of the advanced hormonals"

[gsun]

Would it be prudent to switch for Zytiga to Xtandi?

[Tall_Allen in reply to gsun]

This was for recurrent non-metastatic patients, which is not your situation.

[gsun]

You said this above:

In these trials (PRESTO and EMBARK), metastases were detected with conventional imaging. Now, with PSMA PET scans, many of the patients in those trials would be detectably metastatic, so the results are not surprising. Xtandi and Erleada are known to be beneficial among men who are metastatic and hormone sensitive (mHSPC) and are FDA-approved for that indication:

[Tall_Allen in reply to gsun]

Perhaps I should have been more clear. In PRESTO and EMBARK, they used conventional imaging (CT, MRI or bone scan) to detect metastases. If metastases were detected, they were excluded from those trials. I mentioned Xtandi and Erleada because they were used in EmBARK and PRESTO, respectively. Zytiga has long been approved for newly diagnosed metastatic patients, for metastatic castration-resistant patients, and recently, for high-risk patients with positive pelvic lymph nodes.

[Schwah]

so doesn’t that leave the question of what’s best, unanswered…..Erleada, Xtandi or Zytega with ADT for metastatic hormone sensitive men such as myself? Any thoughts? Or does one switch off time to time?

Schwah

[Tall_Allen in reply to Schwah]

There has never been a randomized clinical trial, and probably never will be.

[Schwah in reply to Tall_Allen]

I know. Yet we all must make our own decisions on which drugs to use. Do you have an opinion based upon the various studies, SE profiles and your discussions with various doctors? Which would you use if faced with the choice?

Schwah

[Tall_Allen in reply to Schwah]

For non-metastatic, recurrent patients with high PSADT? I'd get a PSMA PET to see if it is metastatic. I'd start with Lupron+Erleada or Lupron+Xtandi and see how well I tolerate it (switch if intolerable). From there, make decisions about SBRT to distant metastases (if oligometastatic) and iADT.

[Boywonder56 in reply to Schwah]

From my 5 .6 yrs of being on earleada...titan trial....i can say although admittedly biased that aplutimide should be heavily considerd . Se aside...and the fact thzt it is brain blood barrier crossing..... like a nagging wife you can get used to anything.....bw

[Muffin2019]

If it works, did not for me.

[NecessarilySo]

I wonder if Xtandi monotherapy could be a viable option for some.

[Tall_Allen in reply to NecessarilySo]

It depends what you mean by "viable." It had worse oncological results than the combination.

[Boywonder56 in reply to Tall_Allen]

I would like to interject T.A. that my uro onc...said they are favoring going to a mono therapy like ap or enz. ...that the cognitive effects of long term lupron/ eligard ....antagonist?...are finnaly being realized....he called them poisins....when 6 yrs ago as soc there were little side effects...in his own words....kind of like the drug dealers they are.....theres more money in pills ....just my thoughts...bw

[Blueribbon63]

After Zytiga-prednisone-lupron failed, mostly by overwhelming SE from the first two. I received my second Lupron injection last week even though there's a slight PSA increase from .83 to 1.10 (they did not do a testosterone test, Wich was climbing again) Oncologist mentioned we could start Xtandi but also suggested to wait for my next month labs and see what's PSA doing. I insisted with starting Xtandi right away, MO agreed. RX was approved only to later find out that Xtandi has interaction with Biktarvy. So is a no go for me, and both the oncologist and my PCP are meeting to decide treatment plan. Also, during my visit with Onco I asked to get a DEXA test (not done in more than 3 years.) The results are so vague and inconclusive, no measurements, density percentages, etc. Like it's assumed I already have osteoporosis and they limited the text to measure Kyphosis in a small portion of the spine. My request for you is to share your research on treatment APC 4 met and undetectable HIV (with ongoing treatment) thanks.

[Tall_Allen in reply to Blueribbon63]

This is only about treatment for men who are non-metastatic and recurrent after attempted definitive treatment. It doesn't apply to you.

[anonymoose2]

That’s my finding. For me personally my first vacation was to long. I’m currently on 6 months of Xtandi and Lupron and 2 more months will be on another vacation. This time 5 months instead of 8 if all the numbers line up. I forget the medical term but Castration seems a better choice than taking the Lupron and just going Xtandi.

I’ve seen others take almost 18 month vacations but my cancer is to aggressive. QOL is so much better those months on vacation. Xtandi has been a lifesaver for me twice now. 80 mg is very effective for me.

[Boywonder56]

Orchieotomy......kaliber does em in his garage....

[beogradjanin]

Thanks for the info.

Already in tenth year after diagnosed metastatic prostate cancer (bones and limf nodes), since the begining on ADT alone, than 6 x Docetataxel, and last 36 months on ADT + Xtandi. On my own adding 2 x daily Metformin 1000mg + 1 x Statin 20mg.

Four years ago, after Docetaxel mnaged to drop my PSA from 55 to 5, than it almost imediatelly start rising, so after one year on ADT alone I was adding Xtandi, which imidietely drop my PSA to 6, and then started to rise constantly, now it is 64.

SInce I lived in Serbia, where there are not many options for next therapy, oncologist tell me there is an option of Carbazitaxel when Xtandi will fail.

What are my options in your oppinion, till when to continue with Xtandi, and what to do next?

[treedown]

TA is science saying that these are both better than Zytiga in this setting mCSPC on PET or is there no side to side trial or study? It's become pretty clear to me that I cannot restart Xtandi and will push for Daralutmide or maybe now Apalutamide. That said if Kaiser still won't approve either I will seriously reconsider Zytiga/Pred. again.

[Tall_Allen in reply to treedown]

The setting is non-metastatic on conventional imaging (not PET) and recurrent with rapid PSADT.

[PJ95]

Can Orgovyx be used in lieu of Lupron?

[Tall_Allen in reply to PJ95]

I'd guess so.

[PJ95 in reply to Tall_Allen]

SEs were better in my case, thanks TA