Hmm... Why am I on Zytiga?

[westof]

Here is an email that I sent to my MSK MO yesterday (Dr S is my RO).

I'm blessed to have both of them caring for me. They give me all the time that I need and answer every question I ask, with patience and clarity.

Just want feedback from our great forum.

"Happy (belated) New Year, Doc!

I'm prepping for consults with you and Dr. S on 2/6.

Monthly blood-work seems to be on target and I feel great.

My question is: Why am I on Zytiga?

All the research I've done indicates that it is only used with patients that are, mCRPC or CSPC.

When I first met with Dr S, He seemed to indicate that I was G9, S3 and no mets (according to the scans).

Was it an misunderstanding on my part?

Or perhaps, after HDR Brachy and 25 days of IMRT; Could it be overkill, an overabundance of caution (Hitting it hard and fast)?

Best,

AJ

[Tall_Allen]

I suspect that you are right that they are trying to hit the cancer as hard as they can with a souped up adjuvant hormone therapy. Given the impressive survival benefit for mHSPC, and the recent discovery of benefit in non-metastatic PSA-recurrent patients using it as part of an intermittent ADT protocol (below), there is every reason to believe it is beneficial in high risk patients receiving RT as well.

urotoday.com/conference-hig...

MSK is the lead investigator of the AASUR trial, which gives Zytiga and Erleada to very high risk men receiving RT. The results are expected in May, but they may already be aware of a benefit;

clinicaltrials.gov/ct2/show...

If you "feel great," why not stay the course?

[westof in reply to Tall_Allen]

Hmm... Hey T_A, I was hoping ( and perhaps expecting) that you would be the first to reply!

Thanks!

Given the fact that I've made it to 71 and I'm active and really do feel great, There is no reason to discontinue the plan.

Many Thanks!

Best,

AJ

[timotur in reply to Tall_Allen]

TA: neither of the studies you linked apply to westof-- he is not recurrent and had prior Brachy tx.

link #1: applies to recurrent PCa (which suggests HSPC transforming to CRPC).

link #2: Brachy tx is exclusionary to the trial (i.e. Brachy could have been curative).

So those don't really apply to his profile.

[westof in reply to timotur]

Hmm... Hey Tim,

I've read both of your replies (to me and T_A)

But lets face it: I'm not that smart!!

However, I've printed everything and my MO consult may go into extra innings!

Best

[timotur in reply to westof]

Great, let us know what he says. I think there is no right answer, because we had ADT + Z adjunctive to Brachy, which is exclusionary to the major trials. Thus, statistically speaking, we can't really infer anything from them.

[westof in reply to timotur]

Thanks, I will report back, as much as I can remember. Although, I will take copious notes!

Best

[Aynoy in reply to westof]

What is your dosage on the zytiga?

[westof in reply to Aynoy]

1000 mg daily, with prednisone 5mg.

[Tall_Allen in reply to timotur]

No, I didn't say they did. But they do suggest a benefit to adjuvant abiraterone when used earlier. Given that the OP feels good and was somehow able to obtain adjuvant abiraterone, why would he forgo that opportunity? As I said, the doctors at MSK will have access to the most relevant data.

[timotur in reply to Tall_Allen]

He might forego that opportunity to use Zytiga now, and save it for later if he had an unfortunate recurrence, which is the population studied in link #1.

There's really no hard, statistically relevant data on folks that have had prior Brachy, because all the major trials exclude it.

[Tall_Allen in reply to timotur]

I definitely do not subscribe to the philosophy of "save it for later." He is attempting a curative therapy, not something that he knows now will have to be treated later. Resistance evolves more slowly when used earlier. God willing, he will never need another therapy if this one kills off all the cancer cells. If it doesn't work, later, there will be other other therapies.

The reason the trial excludes brachy boost therapy is because they hope that by going heavy on the adjuvant hormone therapy, they can prevent the relatively high level of late-term urinary toxicity caused by the boost. Maybe he doesn't need the extra Zytiga, but if he is feeling great, why would he not take it?

[timotur in reply to Tall_Allen]

Rhetorically: If Westof is M0 and in primary tx, why bank a decision to use Zytiga on studies that were done either for recurrent patients or studies on M1 metastatic patients like CHAARTED that support the kitchen sink approach? The OS benefit cited applies to those groups. He doesn't fit either one.

Are there any studies that show Zytiga adds to OS for M0 patients as primary tx?

[Tall_Allen in reply to timotur]

Because, with no data, we still have to make treatment decisions. If we see a trend in greater benefit when used earlier, it is reasonable to suppose the trend will continue. No evidence of benefit is not the same as evidence of no benefit. Of course it may be wrong, but for now, that is the best guess.

[podsart in reply to Tall_Allen]

I have been trying to sort out “hitting it hard” vs treatment related emergent resistance.

Seems there are two related phenomenon I have read via our groups discussions.

1. The lower Gleason Pca cells are in some balance with the higher Gleason Pca cells.

2. Pca is a dynamic system and will adapt, presumably via mutation, to treatment pressure and become resistant to that pressure.

I remember discussions that intermittent treatment doesn’t result in improved results. However, the paper on “evolutionary “ designed intermittent therapy seemingly solves this problem by applying the treatment to knock PSA back to original levels and the stopping and constantly repeat this “mowing of the grass” strategy, forestalling treatment resistance and not killing off the weaker Gleasons to retain the weak/ strong balance.

I understand in this case the strategy is hopefully curative, thereby ending the problem. Does this all imply a probability risk/reward assessment in deciding whether to use this strategy.

You say “resistance evolves more slowly when used early”. Did I misunderstand the above resistance mechanisms - how does this slow resistance emergence fit?

Given the above, is treatment resistance also proportional to drug dosage?

[Tall_Allen in reply to podsart]

You have to be careful about information you think you are getting from discussions on this site- there is a LOT of misinformation here and I don't have time to review it all.

(1) It has nothing to do with Gleason score.

(2)Cancer cells do adapt to selection pressure BUT that is not the only reason they become castration resistant

(3) Every indication is telling us that early reduction of the NUMBER of clones has a greater effect than selection pressure.

(4) Castration resistance takes exactly the same time to appear with Intermittent ADT as with continuous ADT

[podsart in reply to Tall_Allen]

Thanks , good info

I was using hi /low Gleason as shorthand for a more or less aggressive Pca cell — but I guess the idea that in a tumor the low aggressive Pca cells have some form of controlling/balancing influence on hi aggressive Pca cells is an invalid concept

[Tall_Allen in reply to podsart]

Various cell types communicate and influence one another.

[Flyboy180 in reply to Tall_Allen]

How do you know point #4, exact length of time for resistance?

[Tall_Allen in reply to Flyboy180]

Because there have been several randomized clinical trials comparing intermittent to continuous ADT. They all show the same thing.

[westof in reply to timotur]

Hmm... Jeez guys, as an "OP", I really resent being referred to in the third person!!

However, I'm a lucky guy.

Background is finance and was forced to retire in 2010, after the crash.

However, " my darling wife of 46 years" decided to go back to teaching (after being a stay at home mom for 20 years) and it was a Godsend!

Anthem picked up almost 500k of my 2019 med expenses and my out of pocket was a measly 4k.

Best

AJ

[Kaliber in reply to westof]

👍👍👍

[timotur in reply to westof]

You're doing great AJ, glad you worked out the insurance with the help of your supportive wife. I'm also benefiting from my wife's insurance as I'm a retired CPA and she is a medical researcher. Anyway, best of luck with your upcoming appointment, will be interesting to see what they say.

[StayingOptimistic in reply to Tall_Allen]

I was offered this trail about 2 years ago at MSK and declined to receive it. I am not sure if I did the right thing on not based on what TA has said above.

[timotur]

Westof: that's the the million-$ question I'm trying to figure out, i.e. whether to restart Zytiga after dropping it in August due to high BP midway through IMRT.

I discussed this with my local Uro, who prescribes to the thought that Zytiga adds to OS. I mentioned to him that the trials supporting ADT + Z didn't really apply to me as T3N1M0 +SV on several counts, (1) the big one is that prior Brachy tx is exclusionary for all these trials (because Brachy could be curative ex-ante), and (2) the trials were top-heavy with G> 8, M1 metastatic participants. He sort of nodded to all of these, but said the trials still were suggestive that Zytiga adds to OS even in nmHSPC. Added to the above is the 2018 Aagarwal study showing Zytiga is associated with a risk of "treatment-emergent" small-cell NE PCa in mCRPC, which poses the question, does it pose the same risk for nmHSPC?

So, I've pretty much decided not to risk going back on Zytiga-- I don't like the added toxicity of high BP when I've had heart palpitations in the past. I will discuss with my MO in March, and get some more feedback then. Meanwhile, it's eight more months of Lupron which seems to be doing the job, as my PSA continued to drop from 0.03 in August when I dropped Zytiga, to <0.01 now.

[Hidden]

By bp went up and I hit with meds then it moved up so I doubled it and I’m back to 120/70. I’m glad I’m going off the Zytiga soon. I’m tired.

[westof in reply to Hidden]

Hmm... Hey Carlo,

I started Zytiga and prednisone in March 2019,after starting with Casodex and Lupron on 8/18.

BP did go up, during and after HDR Brachey and IMRT and Zytiga!

However, I've been taking Valsartan HCT 160/25 (for years,mild hypertension) and added Flomax (another diuretic).

I put the BP cuff on every day and my average results are 110/70.

Best,

AJ

[DeanNelson]

It’s not the Zytiga I worry about anymore the

Lupron absolutely smashes my quality ofLife.

[westof in reply to DeanNelson]

Hmm... Yea, I get it Dean. However, I'm due for my 6th quarterly injection next month and Libido loss and ED are my only SE's.

Best

[DeanNelson in reply to westof]

Do you get 6 months or 3 months?

[westof in reply to DeanNelson]

3 months

[Ramp7 in reply to westof]

Going for my first Lupron 3 month shot tomorrow.

[westof in reply to DeanNelson]

Hey Brother Dean,

Here is a bio of my MO. Perhaps you may be able to glean a nugget of alternative therapy, to help you with your pain.

best,

AJ

thehour.com/entertainment/a...

[westof]

Hmm... My MSK MO just replied to my email:

HI AJ

In the non-metastatic setting, prostate cancer that is considered high-risk and meeting 2/3 criteria: T3 or T4 primary (yours was T3 by MRI), PSA >40 (yours 25), Gleason 8 or higher (your 9),

Qualify and live longer when treated with zytiga and radiation/leuprolide per Stampede trial.

R