Studies showing life extension: Lupron/ Zytiga/Pred combo ?

Have any Studies showing life extension using Lupron/ Zytiga/Pred combo as compared to doing Lupron only, until it stopped keeping PSA repressed (Lattitude study)?

My question is: What about adding Zytiga and Prednisone to my Lupron now while the Lupron is still working (I started it in Aug 2106 and now coming off a "holiday") Got a shot two days ago. The other option is Start the Zytiga and Prednison with the Lupron when the lupron starts failing by itself. My oncologist seems to like the second option there. I said I'd like to be aggressive but Im not sure that there is any evidence showing that doing all three now is better for longevity than stairstepping (Lupron now and then adding Zytiga/Pred after Lupron fails.

I'm trying to decide whether to be "more aggressive" now and use all three but lowering my quality of life and not being allowed to take any breaks/holidays, like is possible with Lupron only. This leads to my next question:

If breaks/hoidays from Lupron only treatment yields equal lifespan as continued Lupron regime, then wouldn't taking breaks from the Lupron/Zytiga/Prednisone be similar in concept and breaks should be allowed?

Lastly, is anyone using Lupron, Zytiga, Pred experienced problems with their heart or coronary arteries due to the triple treatment?

thanks in advance,
George

Allen,
Is it fair to say that if you had radiation to the pelvic bed and pelvic lymph nodes AND then you become BCR, the PCa has clearly become distantly metastatic?

thanks TallAllen, I read the results of those studies you mentioned but I don't think they have compared taking Lupron zytiga and pred VS. doing Lupron first and then zytiga and pred added to the Lupron when the Lupron starts failing.

The Lattitude study compared the triple treatment simultaneously against Lupron without zytiga ever being added when the Lupron started to fail.

You see what I'm saying? How do we know that doing Lupron to failure and then adding zytiga and prednisone isn't just as good as starting all three at the beginning? Stampede and Lattitude did not test/compare those two options.

George

George,

You are incorrectly assuming that those who started with Lupron only did not later have second line interventions. In fact, most (74+% in STAMPEDE) of the men in the Lupron control group did have Zytiga or other second line interventions after they became castration resistant. So the proper way to look at it is the studies compared those who started with Lupron only to those who started with Lupron plus Zytiga/prednisone. Naturally, few, if any, men had the initial drug(s) only within the median 40-months of follow up, unless they died before a second-line treatment was used. Second-line treatments may have been any of five: Zytiga, Xtandi, Xofigo, Taxotere, and/or Jevtana.

James et al. said...
Among the patients in the control group (i.e., patients who received androgen-deprivation therapy alone) in the STAMPEDE trial who died of prostate cancer, 74% explicitly reported that they had received one or more of these five therapies. Data on second-, third-, and fourth-line treatments are increasingly difficult to collect and thus are underreported, so true rates of exposure to these therapies will be higher than 74%.

The double-blind, placebo-controlled LATITUDE trial produced strikingly similar outcomes with different patterns of care after relapse; this suggests that differing patterns of care after relapse between the STAMPEDE and LATITUDE trials were not important drivers of differences in survival.

Furthermore, among patients with relapsed disease who had not received previous chemotherapy and who received abiraterone in the COU-AA-302 study, the median progression-free survival was approximately 16.5 months, and the median time to treatment failure in the control group of patients with M1 disease in the STAMPEDE trial was approximately 11 months, so the estimated time to abiraterone failure was 27.5 months. In comparison, the median failure- free survival with first-line abiraterone among patients with metastatic disease in the STAMPEDE trial was approximately 54 months.

Todd-
As you can see, our posts landed here at exactly the same time (5:16 PM) and both were addressed to George. I just added George's name to my post to clarify. Of course Lupron must be continued - no question about that.

Thanks to you Allen and Todd, In response, I have a couple questions:
1. Are you saying, never stop the Lupron even during the Lupron only phase? aka Intermittant Lupron, which MD Anderson and Duke said I could do because life expectancy was the same for continuous Lupron or intermittant Lupron. OR are you saying, continue the Lupron when it stops working and then add the Zytiga and Prednisone?

2. If you stop Lupron on an intermittant break/holiday, does it matter when to start on it again wrt your rising PSA - for example - before it rises to 1 or 4 or 11 in my recent situation?

3. If (not sure if you do) you support intermittant therapy, could you do intermittant therapy effectively with lupron/zytiga and Pred, just like Im doing with lupron alone? This doesnt seem to be a common recommendation among doctors now, however, my doctor at one of the top hospitals just told me to start the Zytiga, lupron. pred combo for four months and we could evaluate and decide whether to take a break or not.

4. Would stopping and starting the zytiga/lupron/pred cause stress and deterioration on my coronary artery disease, worse then just staying on the drugs continously? One doc told me that hapens when you do intermittant lupron.

I'm just trying to do what makes the most sense.

thanks for your time and thoughts.

George

George-

It would help a lot if you added a signature with your treatment history and current status. Answers to your questions depend on those.

So Allen, to put it in simple terms, adding Zytiga to Lupron at the front end worked nearly twice as long (54 months vs 27.5 months) compared to adding Zytiga on the back end. Do I have this right?

thanks for all the replies. TallAllen, good point, I'll add my details now.

George

George-

Thanks - that helps.

I don't know if that abdominal LN met can be irradiated safely - but you can certainly discuss with an RO.

George said...
What about radiation, does it extend longevity based on studies/evidence on metastatic cancer, or does it just lower the psa for a short period without actually extending lifespan?

Great question! So far there is no data on extending survival, and what there is is equivocal. There has only been one randomized trial, and it was just a pilot study. And they were not looking at whether it extended survival, only if they were able to delay starting salvage ADT based on whack-a-mole treatment of 3 or fewer mets. They defined the trigger for salvage ADT by the appearance of 3 simultaneous mets. So the control group only had to evince one more met, while the whack-a-mole group had to evince 3 new mets at the same time. Even using this biased trigger for ADT, whack-a-mole only added 8 months before ADT treatment had to be initiated, and even that was not statistically significant with 95% confidence (they widened it to 80% confidence because they intended to pursue an expanded trial anyway).

Here's more about the trial:
/pcnrv.blogspot.com/2017/12/metastasis-directed-therapy-for.html