February 1, 2023

Prof Karim Fizazi speaks to ecancer about the overall survival with abiraterone acetate plus prednisone for de novo metastatic castration-sensitive prostate cancer in the PEACE-1 trial.

I was very happy to present the data of a piece one phase retrial at the esmo congress in paris uh the background for peace one is that for a very long time the standard of care for patients with the nervous metastatic prostate cancer was underneath operation therapy alone as we probably all know it has changed in the last five years or so the stack cell was shown

To improve survival venable right run with together with some other agents next-generation hormonal agents such as enzalutamide or apalutomide and then radiation therapy directed to the prostate primary was also shown to improve our survival before piece one what we didn’t know was whether we should combine all these treatments together or at least some of them

And this is really why we did the trial so basically the design of piece one is a two by two design large phase three to all 1200 men have been randomized and patients receive standard of care most patients uh received endogenous therapy plus the stock cell as the standard of care and they were randomized to received either this alone or combined with aberration

Or combined with radiation therapy or both aberration and radiation therapy on top of standard of care with adt plus dos taxa again it’s a two by two design and we’re looking at two co-primary endpoints one is not nature as i’m speaking this is about the role of radiation therapy on top of an intensified systemic treatment and i’m saying it’s not mature because

For the radiation therapy question we are focusing on patients with low volume disease so we will need to be patient and look for longer follow-up before we have enough events uh and before we can analyze the trial for the radiation therapy equation but we have indeed enough events to look at the other co-primary endpoint of the trowel which is the efficacy of

Aberratran when added on top of androgen deprivation therapy and the stock cell with two endpoints radiographic progression for survival and overall survival for these patients before the summer we reported the first data from the trial which was about radiographic progression for survival when aberration is added on top of adt plus the stack cell for these men

With the nervous metastatic prostate cancer and indeed our pfs data were significantly and clinically markedly improved with aberration used invest triplet combination the median time to progression radiographic progression or death was two years in the control arm and it was improved to 4.5 years in the experimental arm when a barrage one is added so two and

A half additional year without progression or death for this patient which obviously is huge difference now here at esmo we updated the data and we were able to analyze overall survival and i’m happy to say that we show that not only rpfs is improved but also overall survival with a 25 percent reduction in the risk of death favoring the triplet combination with

Adt plus the stacks and aberration for patients with high volume disease thus translate into approximately an 18-month absolute difference in overall survival which is of course big for these patients for men with live volume disease will need a longer follow-up before the medians are rich of course most of these men were still alive when we perform vinolysis

So this was achieved in a context where side effects do not seem to be an issue we saw the traditional side effects associated with aberration investoral hypertension hypokalemia and transaminase increase no real difference regarding other side effects so new synergistic toxicity if you will when added to chemo hormonal therapy which is of course very restoring

To a patient so based on that background i think uh we now have a new standard of care at least for patients with high volume disease with adt plus the stack cell and aberration so based on this data from piece one i think we should change all the standard of care at least for men with the nervous metastatic disease and high volume and adt plus the stack cell

Plus cyber return should be proposed to these men when they’re fit enough for chemotherapy the good thing is that those drugs are mostly generic almost everywhere on the planet and the right one will soon become generic as well in europe so this should become very cheap for either the society of insurance of a patient if he has to pay out of pockets this is this

I think very important now looking uh forward to the future i think we should stop looking at the never metastatic prostate cancer as just one disease and we should ask different questions according to the biology of the of the disease for example for men with bracket ii or brachii one alteration we should wonder whether we a pop inhibitor should be introduced

Early in the course of a disease and some trials are starting asking this data also for patients with oligometastatic disease we should also evaluate whether local treatment towards the metastasis with radiation therapy should be used and again randomized trials are underway psma targeting should be also tested and for men with a p10 loss we should also go for

Akt inhibition in randomized trials so all this is about to start or has already started which is great for the future because these men are still dying and we really want to continue the progress

Transcribed from video
Overall survival with abiraterone acetate plus prednisone in PEACE-1 By ecancer