Is early intervention with abiraterone (Zytiga) in addition to standard ADT beneficial?

I’m linking an article below from urotoday.com dated November 2017 that is well worth reading by any of us who are in BCR after initial treatment. It caught my eye because it relates to and mentions a clinical trial in which I am currently enrolled.

This is an overview article “The Five-Take Home Messages of the LATITUDE and STAMPEDE Studies” – not a published study or trial. It offers a brief overview of these two studies and then discusses what the studies’ results may suggest for treatment of patients with either metastatic or seriologic (what we call BCR on this forum) recurrence.

Both the LATITUDE and STAMPEDE studies were done using abiraterone (Zytiga) on patients who had not previously been treated with standard ADT. All patients in the LATITUDE study already had high-volume metastatic PCa. The STAMPEDE included patients with bone mets but also include patients who had only positive lymph nodes and also patients who had no detectible mets or nodes but who had other high risk factors -- stage 3 or 4, PSA over 40, Gleason 8 to 10.

There is a lot to consider in this article, not the least being that the author’s ‘take-home messages” are just that – messages, not conclusions – he parses suggested trends and avenues for further study from these two trials.
Of particular interest to me was his message no 1” Yet more evidence that earlier intervention is better” This is where he mentions the study in which I’m enrolled: “Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer.” The goal of this trial is to shed light on whether early intervention with either or both abiraterone or apalutamide may confer any benefit in addition to standard ADT (Degarelix a.k.a. Firmagon) in terms of overall survival or failure-free survival.

I enrolled in the “Androgen Annihilation” trial after washing out as a candidate for the Prostvac vaccine trial because my doubling time suddenly began accelerating and pushed me out of the Prostvac trial's inclusion criteria.

As it happens, I was randomized into the Degarelix-only group of the Androgen Annihilation trial, so what I am getting amounts to the same standard treatment I’d be getting if I weren’t in the trial other than some additional blood tests and scans. I’m not disappointed to be in this control group. I wasn’t looking forward to the added SE’s of Zytiga plus prednisone, though I was hoping to get into the intermediate arm of the trial which included Apalutamide along with Degeralix but not Zytiga.

Another reason I’m not disappointed in being in the trial’s Degeralix control arm relates to the authors’ discussion further on in the article of the yet-to-be learned unknowns having to do the sequencing of standard ADT and these newer treatments. I wonder if using an everything but the kitchen sink approach at the outset may leave less to work with down the road. Maybe yes. Maybe no. Maybe down the road is significantly postponed.That’s why they do studies.

https://www.urotoday.com/center-of-excellence/mcrpc-treatment/from-the-editor/100084-the-five-take-home-messages-of-the-latitude-and-stampede-studies-charles-ryan.html
Jim

Are the insurance companies going along with this ? They usually have the final word unless you can pay for your cancer treatment out of pocket..

Reading through my post, I just realized it may be confusing. In the 2nd paragraph I am using “early” in the context of starting Zytiga/ Lupron at a lower PSA. I’m delaying the treatment of starting the two drugs together as long as possible.

Fairwind,
I hear you about our friends the insurance companies. I would hope that if studies show earlier use is effective they would have to come around and cover it.

Metamax,
I see your June PSA was 22.3. Your signature shows RALP plus adjuvant in 2015. Did you have any ADT along with the RT? It looks like you are now planning to start directly on Zytiga and standard ADT together? Just curious and trying to get my head around the different combinations and sequences of treatments.

Treatment options are pretty well knowable up until we hit the point where initial treatments and maybe initial salvage treatments have failed. From there on everything starts to get murky. Kind of like old-world explorers who have a compass, a sextant, and few crude maps.

Post Edited (Bohemond) : 10/22/2018 10:03:14 AM (GMT-6)

Bohemond,

I wasn't on ADT at the time of salvage RT and I'm glad I wasn't, because in retrospect it is clear that I was systemic at the time of RP. Hopefully the debulking theory has merit, and my RP wasn't a wasted effort. I agree that post-primary treatment is a murky area requiring some intuition from an experienced MO. My first MO was not interested in any input from me. My current MO is 70 years old and has been on America's Best Doctors list several times (if that really means anything). He goes to all the conferences and is up to date. Like Newspaperlover's doctor, he is very sensitive to my concerns, thoughtfully answers every question I have, and he tells me what he thinks. For example, he completely shot down my Casodex monotherapy proposal as an unethical therapy. I'm not a “survive at any cost” type of guy and QOL is as important to me as overall survival. My PSA currently is 28, but I don't like to advertise it because it tends to freak people out. I have had four bone and CT scans and there's nothing showing yet. I know that once I go on Lupron/Zytiga I'll likely be on it the rest of my life, so I want to delay that as long as reasonably possible. I was scheduled to go on the drugs in September but my PSA velocitiy significantly slowed, so we're going to see what the next PSA in December shows. My MO noted that most of his patients elect to go on the drugs earlier because, for them, having the thought that they are “doing something” helps to reduce their anxiety. He says that nobody really knows if there is an advantage to starting the drugs earlier or later. My MO said he would ideally start ADT just prior to the mets causing problems, but there's no way to predict that. His definite criteria for starting ADT are the presence of any of the following conditions:

1) High PSA velocity
2) Spots on scans
3) Physical symptoms

One good outcome for my decision to delay ADT, pointed out by my MO, was the finding that for people in my situation, starting ADT using both Lupron and Zytiga conferred a significant lengthening of the time to castration resistance. Had I started ADT earlier, and using Lupron alone, I would have missed out on this important finding.

Sorry about the long winded post, but it's a long winded topic.

Mattamx,

I respect your decision, and your MO's concurrence, to let PSA increase to your current levels. Not sure I would have that level of determination. The three criteria your MO would use in starting ADT are very helpful to me as a framework for my next discussion with my MO. As I understand what limited studies show so far about abiraterone is that treatment is supported only when hormone resistance is noted, and hopefully before mets are revealed. Kind of a "narrow" window. Myself, as long as I don't experience one of the three issues noted by your MO, I would like to avoid ADT and its SE effects as long as I can. Your post is very helpful... NewspaperLover

Zytiga showed OS benefits comparable to Docetaxel when used as a front line treatment (prior to castrate resistance) in a landmark study reported last year in June

Thanks Jim,

It is very inspiring to hear that you are having minimal side effects. I’m not concerned about sexual side effects - that went out the window with surgery and Peyronies. I’m primarily concerned with survival, and QOL as I survive. My worries with ADT are brain fog, fatigue, and generally feeling like crap. The past few years on HW I’ve read ADT threads hoping to see guys report the side effects weren’t as bad as they thought it might be. Those reports do happen occasionally. Your post gives me additional hope that when I go on ADT I could be one of those guys.