Nubeqa Monotherapy vs Dual Therapy with ADT

@jeffmarc In the LIBERTAS trial, "intermittent" means stopping ADT and continuing with just Apalutamide unless/until PSA hits 10.0. That's for mCSPC, specifically.

@jeffmarc I'm on Apalutamide and have no side effects beyond the normal ones from my ADT. That's the challenge with anecdotal evidence: the people you're hearing from aren't randomly selected.

The clinical claim for Darolutamide is that it has fewer cognitive side effects because of the blood-brain barrier thing, but that doesn't eliminate the risk of other types of side-effects (cardio, digestive, liver, etc).

Fortunately, severe side-effects are relatively uncommon with all the -lutamides, so most of us are dealing mainly with the ADT ones.

Darolutamide + ADT doesn't seem to increase the risk of brain fog v.s. ADT alone, while Apalutamide may raise the risk by a couple of percentage points, but brain fog from ADT still overshadows any from the ARSI. That's why there are studies underway to see if we can do without ADT and continue on just the ARSI.

Also, with the first generic -lutamide (Enzalutamide) coming as early as next year, watch for both Johnson and Johnson (Erleada) and Bayer (Nubeqa) to go into research and marketing overdrive to protect their high prices.

If generic Enzalutamide becomes available for $1,000 (or even $100) per month, it's going to be much harder for J&J and Bayer to convince U.S. insurers to pay $12K–15K per month for their -lutamides.

Expect a flurry of new research papers, press releases, and expert presentations as part of massive lobbying blitz over the next year, leaning heavily into small (but supposedly, essential) advantages of Erleada and/or Nubeqa. If a friendly research expert comes to your support group to talk about one of them, it's *not* coincidental. 🙂

@stage4lovolmetpc
As I mentioned in a few other comments in the last couple of days, I know a lot of people that have switched to just Darolutamide And it works just great for them. Over at the ancan.org Advance prostate cancer Group there are a few people that have already done this and have no problem at all staying undetectable. I’m not saying it will last forever since these drugs never last forever, But Daro hasn’t been out all that long and No one has reported it failing.

I’ve been participating in a Healthunlocked forum in the last few months and one of the first people to send me a private message was a guy who used to be in an online forum I attend twice a month.. He moved to South Africa, but switched over to Darolutamide as his only drug and it works just great for him. He has a very severe case of prostate cancer and is in his 80s, and he’s quite pleased with it. He had to mention it to me after I had promoted Darolutamide on the forum.

18 months ago my oncologist and I figured my testosterone would never come back since I had been on ADT for six years and I was 77. I stopped taking Orgovyx for 8 months. My PSA stayed undetectable since I was still on Darolutamide. Unfortunately, my PSA went up to 50 and my oncologist wanted me to go back on Orgovyx since I have BRCA2.

@northoftheborder
Just do a search on the web for fatigue and apalutamide. This is what I have heard from some people in online forums. If you were attending ancan.org Advance prostate cancer meetings you would hear them recommending people switched to Darolutamide In those cases.

Fatigue is a very common side effect of Apalutamide (often prescribed as Erleada), which is typically used alongside androgen deprivation therapy (ADT). While extreme tiredness is frequently reported, clinical data and user experiences indicate that it can be highly manageable with regular monitoring and lifestyle adjustments. NIH

@northoftheborder
Then we look into the definition of intermittent, “ occurring at irregular intervals; not continuous or steady.”

The LIBERTAS Study “intermittent use of androgen-deprivation therapy (ADT) in participants with metastatic castrate-sensitive prostate cancer (mCSPC) who reached a prostate-specific antigen (PSA) level < 0.2 “

By intermittent they mean if the PSA goes above that they would start back up ADT. It’s not a permanent ending, though it could be for some people. The study specifically says it is studying intermittent versus continuous use of ADT.

@jeffmarc As far as actual cognitive impairment goes, fewer than 10% of patients experienced it on any ADT+a lutamide combination according to one study:
https://dailynews.ascopubs.org/do/mental-health-and-cognitive-toxicities-androgen-receptor-signaling-inhibitors
It does support your general point, that Darolutamide appeared not to increase the risk of cognitive impairment:

ADT alone: 3% risk
ADT + Darolutamide: 3% risk (small increase, but within margin of error)
ADT + Abiraterone: 4% risk
ADT + Apalutamide: 5% risk
ADT + Enzalutamide: 9% risk

Note that they had a paucity of studies to review for Darolutamide (that was a caveat in the findings).

These numbers are very low compared to the impression you might have, but that's what I meant by selection bias: people who have no cognitive issues with ADT + ARSI are much less likely to show up in an online forum or support group looking for help.

And for the small minority who did have cognitive impairment on another ARSI which cleared up when they switched to Darolutamide, they probably felt a general sense of well-being overall once the fog cleared.

@northoftheborder
Not sure those percentages really hold up, Though Apalutamide was much better than Enzalutamide.

The study showed Enzalutamide users had a 3.66 times higher chance of Cognitive impairment than somebody without the drug.

In the case of Apalutamide it was 1.76 times more likely to be a problem, though the range varied from 1.08 times (not really significant) to 2.87 times (significant).

As for cognitive impairment, a network meta-analysis of 15 prospective trials showed that compared with ADT alone, enzalutamide had the highest risk of cognitive impairment (odds ratio [OR] 3.66, 95% CI [2.84, 4.73]), followed by apalutamide (OR 1.76, 95% CI [1.08, 2.87]) and abiraterone (OR 1.64, 95% CI [1.01, 2.45]).14 Darolutamide was not associated with an increased risk of cognitive impairment compared with ADT alone (HR 1.11, 95% CI [0.51, 2.39]); however, only 1 of these 15 trials included darolutamide.

I was out to dinner with a guy Sunday night who had just started Orgovyx Two months ago, He already noticed some brain fog issues with remembering names. ADT seems to make it worse.