New info presented this morning at ASCO - Enzalutamide (Xtandi) worked best in men with mHSPC with a low volume of mets, and in men who did not plan to have early docetaxel (which is probably much the same thing). Apalutamide worked well regardless of high or low volume of mets. However, enzalutamide was compared to antiandrogen (e.g., Casodex) +ADT, while apalutamide only had to beat ADT alone.
More details here:
I had to look up mHSPC. So I thought I would post this;
Métastatic hormone-sensitive prostate cancer
Tall_Allen
To what extent, if any, might we factor in the following: "However, enzalutamide was compared to antiandrogen (e.g., Casodex) +ADT, while apalutamide only had to beat ADT alone."
What factors might cause us to still prefer apalutamide? Under what conditions?
You have to decide based on available data.
Tall_Allen
There doesn't seem to be much in the way of available data, is there?
Attempting to find logic in complex biological systems that have evolved over billions of years is not a recipe for success.
Just wondering what informed speculation you might have on the subject.
The apalutamide test had a lower bar.
I think price and doctor kick-backs will determine which drug gets prescribed...Also, with Xtandi, not having to take Prednisone is a plus, a big plus for some guys...
prednisone given with abiraterone for mHSPC is just a replacement dose, and shouldn't enter into the decision if monitored correctly.
Hi TA,
So, does this mean Apalutamide will be approved for mHSPC with metastasis?
And, now Enzalutamide will be an alternative option from Abiraterone? This is of high interest for me, as it will make ADT vacations viable while still taking Enzalutamide.
I think the FDA will fast track both for approval within a few months. I don't understand why abiraterone vs enzalutamide makes a difference in your iADT, although they haven't been tested for that use.
The rationale is Enzalutamide is an antiandrogen, therefore increasing testosterone would be tolerated while iADT.
The enzalutamide is used with ADT, so there shouldn't be a testosterone increase during the "on" part of the cycle. During the vacation, both ADT and the other drug (whether abiraterone, enzalutamide, or apalutamide) are discontinued, allowing testosterone levels to recover.
Interesting, enzalutamide is not stand alone, requires pairing with leuprolide. My excitement for enzalutamide is dead on arrival.
Although, understand, some combinations of drugs cause efficacy with individuals. We are still in the dart board strategy for treatments...
Well said!!! Mixing cocktails and throwing darts in the dark!!!!
In a very small, retrospective study among men who were metastatic and castration-resistant, abiraterone alone was able to shut down testosterone production even without ADT:
abstracts.asco.org/239/Abst...
Will this be validated in a larger trial? Can enzalutamide or apalutamide be used alone? All good questions - we can only guess.
The EMBARK trial has three arms, one is enzalutamide monotherapy. So next year we may learn if you can take Xtandi without Lupron.
Makes me wonder how that works. Naturally about anything works better when the workload is easier. I have widespread mets, my mets have mets with a starting psa of 1400 - 1600 and now after 5 months on lupron - xtandi my psa is less than 0.2 with a large reduction in my scans ( shrinkage) It’d be hard to have better results of course. In my case it’s not xtandi alone so don’t know how that changes things. Hopefully I can switch to the other one if I’m not castrate resistant by then. The more solutions the better. Even with the truck load of side effects, for me, it’s always better to wake and complain about them than the alternative. Yayahahaha
Actually, docetaxel for mHSPC works for high volume of mets, but not low volume. Your experience with Xtandi shows that individual results may differ from the average results.
Roger that Tall, preciate it. 👍
This is why i didn't get the docetaxel but gourd dancer destroyed his cancer with the docetaxel when he had low volume like me. Now i wish i had tried the docetaxel.
IMHO, a comparison of abiraterone acetate to the other 2 is in order....using ADT + drug......... any idea when head to head study will happen?? Also, while Yonsa is $10,000--the generic abiraterone acetate is way cheaper--the insurance industry will be pushing for that I am sure.... Thanks for posting...
Fish
Fish,
Yonsa is a different implementation of abiraterone, it has different dosage instructions from Zytiga. So, it's not a generic form of Zytiga specifically. For example, I'm taking generic Zytiga from Mylan, it has the exact same dosage, each tablet is 250mg, so take four -(1000mg).
drugs.com/medical-answers/d...
Familiar with Yonsa--the formulation is different and the price also...I question whether the difference in formulation warrants a price that is $7,000 a month higher than the generic...
Fish
Ah, yes, why head to head with Zytiga, perhaps because less restrictive dose instructions.
"generic Zytiga from Mylan, it has the exact same dosage"
What is the difference in price between Zytiga andn "generic Zytiga from Mylan"
For me with blue cross the difference is 200 per month cheaper than brand name.
I have Aetna PPO in Massachusetts, first got Zytiga (janssan) , patient portal listed it as $10k. Then Aetna changed to Generic, Mylan, listed as $7k, anyway, get it at 0 copay.
Do you have less side effects with the Mylan drug than Zytiga. I had way less hot flashes. My fatigue is the same. Actually because it was different I went back to Zytiga.
To be honest, have not noticed any difference, although while on Zytiga was taking 10mg Prednisone and having high anxiety and depression because of the newly diagnosis of stage 4 metastasis and PSA 1000+.
Now taking 5mg, which is so much nicer...
Are you saying for you that the mylan generic is gentler with side effects than the original..... at least for you?
Yes it was different. Less hot flashes. I think the ongoing fatigue has always been the lupron. I didn’t like the change personally so I changed back. Hot flashes made me think it was working better and weren’t that bad. If they make a big change in the price I’ll look at it again. My Dr assured me it was exactly the same and preformed as an equal.
I’m on 5 mg predizone
I think this is pretty important. Please consider starting a fresh post on this subject, and Yonsa as well.
It’s just my opinion and was only on it for 2 months. You start it up and I’ll say what I know. Yonsa is nothing I know about except that it is a new drug. Not generic. Mr Allen will have all the specific info.
Please comment at this link on your experience with Zytiga, generic abiraterone, and/or Yonsa:
Please comment at this link on your experience with Zytiga, generic abiraterone, and/or Yonsa:
Isn't Aytiga brand manufacturer Janssen Biotech? I thought Yonsa is generic also. I guess that is incorrect. Interestingly I am about to start Abiraterone and the hospital specialty pharmacy quoted me $9331 for Mylan Labs while my Plan D provider has me going to CVS or their specialty pharmacy and both quoted me $4486. CVS is Mylan also, while Aetna specialty is Apotex labs. It makes a more than $200 per month difference when the catostrophic coverage activates in 2 months. Janssen's zytiga is not permitted on the formulary but Jefferson told me it was north of $15k per month but I don't know whether they really knew the answer.
My CVS Specialty Pharmacist told me on Friday that Janssen now has their own generic version of Zytiga to compete in the marketplace. Wholesale cost was within $25 of Apotex. I have found no info anywhere to verify what she told me.
Use a Good Rx coupon--go to the website....around here it is $2,600---$3,000 a month with GoodRx--worth looking at if you have co-pays...
Fish
Do you know if the money spent on Good Rx counts toward the Donut Hole?
STAMPEDE has a head-to-head trial between Zytiga and Xtandi. I don't know the expected completion date. They also did a small head-to-head between Zytiga and Docetaxel and found no difference.
Thank you. Familiar with Stampede trial for comparison of Zytiga and Docetaxol...When I was diagnosed, my MO put me on Zytiga and Prednisone with Lupron from the start...low burden disease.....somehow missed the Zytiga and Xtandi head to head. I am familiar with the K arm of STAMPEDE trial with Metformin which is of interest to me, especially since the Prednisone has jumped my Hemaglobin A1C up from the start. My MO insists on waiting for the results from the K arm, since I am non-diabetic. Needless to say, I cut back on my carbs, exercised, and lost weight. I do take Berberine 1x/ day to help my blood sugar--approved by my PharmD at the clinic. My last fasting glucose on my labs was within normal limits. I plan to take another HgbA1C soon.
Fish
It's not looking good so far for Metformin for PC. There was a Phase 2 trial of Metformin + Docetaxel vs Docetaxel alone, which showed no difference in the % who benefited with a PSA drop of 50% or more, objective response rates, metastatic progression-free survival, or overall survival for patients with mCRPC without diabetes - just increased side effects (diarrhea) from the Metformin.
abstracts.asco.org/239/Abst...
You begin with a claim that Metformin for PCA is of doubtful value, but doesn't this finding indicate only that when COMBINED with Docetaxel there are not significant synergistic effects. Was there a Metformin ONLY treatment arm for non-diabetic patients? Or better yet, a Metformin-statin treatment arm? I realize costs are exorbitant for a clinical trial and my conditions are beyond the real-world constraints facing CT coordinators.
I said, "It's not looking good so far for Metformin for PC." If metformin adds nothing to the efficacy of docetaxel, do you think it has efficacy if used alone? Maybe. So far, it's not looking good.
I wonder how much Metformin people in the trial take? My husband takes them and I'll be interested to see if this has contained his mets which I think some of the research indicates might happen.
STAMPEDE will use a much larger # of patients and that will give us a better idea...I would like to see it with all the major treatments to see if there is a possible synergy with one of the meds....at this point, no one knows for sure....
Fish
In the TAXOMET trial, they took 850mg twice a day
Oh thanks almost double what my husband is taking as a pre-diabetic strategy
Fish,
Do you take gymnema sylvestre for blood sugar management with the berberine (I take both before every meal.) Jane McClellan advocates for it in her book on cancer. Also, do you take a statin or a bio-equivalent? I have been taking red yeast rice for more than 20 years for CHOL management and it has worked very well for me keeping my LDL in the 70's. A physician friend at my employer (medical software company) told me to never let my LDL exceed 100. He never saw a patient present in the ER with a heart attack AND a LDL below 100. He said the Framingham heart study supported this generalization. Mark Scholz, as you may know, advocates using a statin in his book "The Key to Prostate Cancer".
I do not take gymnema sylvestre. I take the berberine only. The PharmD advised it one time a day at night because of some of the meds I am on and the drug to drug to drug interactions with zytiga... I take no inhibitors but take several low level inducers which can increase the zytiga levels to 1.25x normal or so...I do take Atorvastatin and my last LDL was 52. My HDL is almost the same. I have been meaning to read McClellan's book, but I have been busy getting Married in April and honeymoon in May in Israel.... Will take a look at gymnema sylvestre....Thank you...
Fish
CalBear74
Apologies, inducers can speed up clearance...I take them late at night....fortunately they are listed as weak and so far, my results have been great--thanks be to God...inhibitors can increase levels of one or the other drug--I took a very low dose of Phenobarbital initially and my LFT's climbed... one needs to take double the dose of Zytiga to get the same efficacy--quickly D/C'd... I check with my PharmD whenever I add anything...
Fish
I take a crestor and eat healthy. I recently started vascepa and it is very effective. Are you aware of vascepa?
No I am not aware of it. What is the benefit you’re seeking?
It's for lowering triglycerides
Something else to consider..When you have been on ADT for an extended period of time, 3 years or more, Recovery to normal testosterone levels may never happen, the drugs action becomes permanent..This is especially true in older men who suffer a natural decrease in "T" levels..Once your testicles have been shrunk down to the size of raisins, they don't just bounce back in a month or two...
thank you
Here in oz
Docetaxal commenced virtually immediately after diagnosis in conjunction with cosudex
Became resistant within months
Now on enzalutamide with 3 monthly zoladex
Hello Tall_Allen
When i read your and the other comments it make me confused ,i copied your writing in case if it will happen to me in the future ,its a scary development but i'm riched with your knowledge i will say ohh my God about our situation,i will struggle like you until the last day.
Very interesting. I just keep hoping I keep all this information about the various drugs filed away. There are so many. Maybe some inventive person will make up a table with the different drugs and when to use...in the meanwhile I'll just try to keep across it all.
if zytiga fails would an option be to try the Xtandi with Apalutamide
If zytiga fails, the first strategy to consider is switching to dexamethasone. When that stops working, try one or the other, but not both together.
Got it thanks
Hey Tall Allen , what do u think of people self administrating themselves with fenbendazole? It's easy enough to get but the idea of taking something that hasn't been tested much in humans gives me pause (or paws depending on the side effects)
I'd like to hear what he says about this also.
I tried it for one month just before a PSA test that I knew should rise, and it did. Maybe I didn't take it long enough.
I'm agnostic. I think taking an antihelminthic can be hepatotoxic and may interact with other drugs - who knows? Another antihelminthic - suramin - was abandoned because it showed no dose-response and was too toxic at higher doses. Niclosamide was abandoned following a dose-finding trial at UWSeattle, but researchers at UCDavis are conducting a small trial.
Update On My Metastatic Prostate Cancer 
Abiraterone or Docetaxel: Which Is Optimal for Hormone-Sensitive High-Risk Prostate Cancer?
Diagnosed with metastatic prostate cancer 2016.
Advanced Metastatic Prostate Cancer
