Can Erleada/Apalutamide and Xtandi/En... - Advanced Prostate...

Advanced Prostate Cancer

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Can Erleada/Apalutamide and Xtandi/Enzalutimide be used subsequently or is Xtandi ineffective after Erleada stops working?

GeorgeGlass profile image
11 Replies

If someone is castration sensitive and they start/use Erleada until it stops controlling the PSA, is Xtandi usually effective to use following the Erleada, or will Xtandi be ineffective because it works in the same manner as the Erleada? I understand that Erleada is for non-metastatic and Xtandi is for non-metastatic PCx but aside from that, do they work in the same way/ target the same thing or would they be effective to use one and then the other? If these two drugs are for non-metastatic cancer then do they use either of them for metastatic cancer or do you have to use some other drug instead of these two?

Basically, I'm trying to decide if it would be better to use Erleada now and see how long I can go before castration resistance or if I should just go with Lupron alone and then add Xtandi later? Or if you can do both subsequently?

I also get the feeling that Oligometastatic vs metastatic seems to be a guessing game or a predication by my doctors based on PSA levels, when they don't see metastatic cancer in standard CT scans. Thus, even though it may be metastatic, I might be able to take Erleada now, due to the fact that there is no cancer showing up on the CT scans. And is that recommended to do or should I wait until metastatic is confirmed and then start on Xtandi?

I'm aware that there are certain adjunctive meds like metformin that some say could help if they are added to apalutimide or enzalutimide. Nubeqa is a another possibility but the results of it don't appear to be as effective as Erleada or Xtandi, which is why I asked about those two. Zytiga is probably not appropriate for me due to Coronary Artery diseases plaque buildup (30-40% with stable angina, BP is normal, blood glucose around 96). I did not do chemo after initial treatment , so 4.5 years later I am in no mans land and probably wouldn't be offered chemo by doctors. Spot radiation is a consideration but my primary question here is about the Erleada and Xtandi. Thanks

Tangent bonus question - has anyone lowered their blood glucose/ increased insulin sensitivity by using bilberry/blueberry/black currant powder/extract? NIH studies said it was effective in a study they did. I eat very healthy but can't get the ADT induced ~96 glucose level to go lower.

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Tall_Allen profile image
Tall_Allen

For non-metastatic (recurrent?) HSPC, SOC is Lupron or similar. There is evidence that adding Zytiga may be beneficial:

meetinglibrary.asco.org/rec...

There was a trial of Erleada in this situation, but results were equivocal.

Why does your heart disease preclude Zytiga but not the second-line anti-androgens?

I have no idea why you think Nubeqa is not as effective. There have been no studies of it in this situation and no comparative studies.

When there are detectable metastases on a bone scan/CT, Xtandi after Erleada may have some activity, but it probably will not be long-lived. It is best to alternate chemo and hormonals. Between Zytiga and Xtandi, there may be an advantage to starting with Zytiga. A recent trial showed benefit, at least in rPFS, in combining Zytiga and Erleada, but not Zytiga and Xtandi.

prostatecancer.news/2019/12...

Use of second-line hormonals with ADT extends the time until castration-resistance occurs.

GeorgeGlass profile image
GeorgeGlass in reply to Tall_Allen

My doctors did not want to add Zytiga to me based on side effects/QofL and concerns about my coronary artery disease. From my readings the study didnt seem to show a big increase in heart events but my doctor was worried about it, even though he's not a cardiologist and he is a "save my bullets" philosophy MO.

I read an article last week that I shared on this site that said Nubeqa results didnt look as good as erleada and xtandi but rereading it now, it looks like the results are pretty close, and with a lower risk to the heart for nubeqa. Here is an excerpt from the article: "In the phase 3 Aramis trial involving 1,500 patients with nmCRPC that were already on standard androgen deprivation therapy (ADT), adding the Bayer drug cut the risk of tumor metastasis or death by 59%. Specifically, Nubeqa plus ADT exhibited a median metastasis-free survival of 40.4 months, versus 18.4 months for placebo plus ADT. How long the regimen extend lives is not yet known, as median overall survival hasn't been reached, though Bayer said there’s a “positive trend” favoring its therapy.

Analysts seem split on how that efficacy data stand against Xtandi and Erleada in their separate trials. Of course, cross-trial comparisons are problematic, but analysts and potentially doctors often turn to them in the absence of head-to-head studies.

In Erleada’s Spartan trial, median MFS tallied 40.4 months for Erleada versus 16.2 months for placebo; and in Xtandi’s Prosper trial, Xtandi hit 36.6 months versus placebo's 14.7 months."

Thus, maybe Nubeqa is the best option for me, but it do you have to be castration resistant before they will prescribe (and insurance pay for) the three options?

It sounds like Zytiga is the only one that can be prescribed for castration sensitive prostate cancer, is that correct?

"Use of second-line hormonals with ADT extends the time until castration-resistance occurs." - So, some people can get prescribed these 2nd line hormonals while still castration sensitive?

"It is best to alternate chemo and hormonals. Between Zytiga and Xtandi, there may be an advantage to starting with Zytiga. A recent trial showed benefit, at least in rPFS, in combining Zytiga and Erleada, but not Zytiga and Xtandi." So, theoretically, someone could do chemo now and then do zytiga with adt combined, after that, or vice-versa and alternate them, possibly extending the time to castrate resistance? then add the nubeqa later? It seems like there are so many options to which sequence to take.

Is docetaxel an option after 4.5 years on ADT and still castrate sensitive? Is there a concern that it weakens your immune system and overall health?

Tall_Allen profile image
Tall_Allen in reply to GeorgeGlass

"My doctors did not want to add Zytiga to me based on side effects/QofL and concerns about my coronary artery disease. " Some doctors don't fully appreciate that the prednisone taken with abiraterone doesn't add anything to its side effects - it is just a replacement dose to compensate for the cortisol that Zytiga inhibits.

"Of course, cross-trial comparisons are problematic, but analysts and potentially doctors often turn to them in the absence of head-to-head studies." I agree that it is never a good idea to compare two different samples on two different trials, except in a very general way (e.g., they both extended metastasis-free survival (MFS) by roughly two-thirds). To illustrate why you can't compare two trials statistically... both those taking Nubeqa and Erleada had exactly the same MFS of 40.5 months, but the placebo group in the Erleada trial had an MFS of 16.2 mos vs 18.4 mos for Nubeqa. Would you then conclude that Erleada was superior to Nubeqa just because its placebo group did worse? Of course not. I'm sure you can find some grad student who would publish such a thing, but no serious doctor would take it seriously, and neither should patients. The right answer is - they are both very good.

"It sounds like Zytiga is the only one that can be prescribed for castration sensitive prostate cancer, is that correct?" Not exactly. . Nubeqa is only approved for men who are non-metastatic (on a bone scan/CT) and castration-resistant. Erleada and Xtandi are also approved for that. It is a rare situation. Zytiga, Erleada and Xtandi are approved for men who are metastatic and hormone sensitive. (Zytiga and Xtandi are approved for men who are metastatic and castration resistant too). Because you are non-metastatic and hormone sensitive, none of those drugs are approved for you. You may be able to get them on clinical trials. Insurance may approve abiraterone because it's available as a relatively cheap generic, but I think you would have an uphill battle getting any of the others.

"Use of second-line hormonals with ADT extends the time until castration-resistance occurs." - So, some people can get prescribed these 2nd line hormonals while still castration sensitive?" As I said, only if they are metastatic too.

"So, theoretically, someone could do chemo now and then do zytiga with adt combined, after that, or vice-versa and alternate them, possibly extending the time to castrate resistance? then add the nubeqa later? It seems like there are so many options to which sequence to take." I think that for newly diagnosed metastatic men, starting with chemo + ADT and then adding Zytiga will prolong time to castration resistance over the opposite sequence, but that hasn't been proven. Whether Nubeqa has the same kind of cross resistance with Zytiga that we see with Xtandi is anyone's guess. The combination of Erleada and Zytiga prolonged progression free survival over Zytiga alone in men with mCRPC.

"Is docetaxel an option after 4.5 years on ADT and still castrate sensitive? Is there a concern that it weakens your immune system and overall health?" It is an option for men who are metastatic and hormone sensitive. It is a good idea during the pandemic to have Neulasta with it to protect immune response.

GeorgeGlass profile image
GeorgeGlass in reply to Tall_Allen

very good info, thanks Allen. The only issue I have with Zytiga is that I'd have to take prednisone, which as a steroid causes bad reactions for people like me who have been "floxed" long term damage from flouroquinolones, when I took Levaquin last March to fight a virus that I had for three months. 12,000 people on Floroquinolone Toxicity Group on facebook, including Currumpaw on this site have had their lives damaged or totally ruined from these floroquinolones like Cipro and Levaquin. Those people say taking steroids causes a relapse in any progress they made.

My fear of chemo is that my white blood cell levels are always around 3.8 and I wonder how weak my immune system will be if on chemo. I wish there was a way to raise white blood cells but I dont think there is. I eat healthy and exercise but the wbc levels never rise.

Tall_Allen profile image
Tall_Allen in reply to GeorgeGlass

That is a common misunderstanding about prednisone taken with Zytiga. It is only a replacement dose to replace the cortisol that Zytiga takes away. It has no extra activity. You needn't worry about immune suppression.

Neulasta is often given with chemo to increase white blood cells during chemo. It is especially important during the pandemic.

GeorgeGlass profile image
GeorgeGlass in reply to Tall_Allen

Gotcha, Ive seen thousands of the Nuelasta commercials so I'll defienitely take that if I get chemo. thanks.

The prednisone adverse reactions in "floxed" people has more to do with DNA and mitochondria damage that is permanent in a lot of people. You'd be amazed if you looked at that webpage on facebook - "Flouroquinolone Toxicity Group". You'd have to pretend that you were floxed when you try to become a member of the group, or maybe you could say that you are researching for a friend. The effects on me were substantial. For currumpaw his were catastrophic.

Tall_Allen profile image
Tall_Allen in reply to GeorgeGlass

It is immaterial when you are just taking a replacement dose. It's only bringing cortisol levels back to normal.

GeorgeGlass profile image
GeorgeGlass in reply to Tall_Allen

From the study results, do you think any of the four (erleada, zytiga, xtandi nubeqa) are more risky than the others with grade 3or4 events, such as heart attack, high blood pressure or other serious problems?

Tall_Allen profile image
Tall_Allen in reply to GeorgeGlass

I don't know. I'm sure it varies a lot among individuals.

MateoBeach profile image
MateoBeach

Yes chemo would be nest next step. Get your COVID-19 immunization. The infusion nurses know how to make it safe. Better than visiting a friend’s house or restaurant. Then Zytiga is next in the best androgen sequence. But if your MO won’t go there now perhaps you could consult your cardiologist to reassure him. Or if he would be willing to recommend Nubequa for you for possible lower cardiovascular risk you might be able to get it by both your MO and your insurance. Just saying.

GeorgeGlass profile image
GeorgeGlass in reply to MateoBeach

I dont think many people are doing chemo in the middle their treatment progression, right? It's usually right at the beginning or right at the end. Lupron is getting my psa to .01 so they seem to think chemo is not appropriate in the middle, although this view may be starting to change just recently?

Wouldn't chemo cause covid immunity to be destroyed? I lost all my Measals antibodies after getting radiation for prostate cancer. I'm not exactly sure what you mean by this statement: "Get your COVID-19 immunization. The infusion nurses know how to make it safe. Better than visiting a friend’s house or restaurant. " If immune system is semi-weak, it is hard to build antibodies, add chemo to that and I dont think you would build any immunity. Plus, fitness trainers and teachers working from home get priority over stage 4 cancer patients under 70 years old, here in America.

Ya, I'm not getting a clear recommendation on this site for Zytiga, Nubeqa, Erleada and Xtandi. I sounds like they are all considered relatively equal in effectiveness. From my research, it seems like Nubeqa might be safer for someone with coronary artery disease. Anecdotally, I've heard several guys on this site that had to stop Xtandi, Zytiga and Erleada. Haven't heard much about Nubeqa one way or the other.

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