PEACE-1 is a phase III trial testing new treatments on top of standard of care for men with de novo metastatic prostate cancer. Here, during ASCO 2021, we are reporting the very first results of the trial, that of abiraterone in men receiving standard treatment with conventional hormonal therapy plus docetaxel chemotherapy.

Until 2015 conventional hormonal therapy, which is really androgen deprivation therapy, was used as the standard of care for men with de novo metastatic disease. Of course, it typically worked, but not for long, and patients typically progressed after a year or so. Since this time we have been fortunate to see a number of positive phase III trials establishing first the role of docetaxel chemotherapy in the space and then data for next generation hormonal agents – abiraterone, apalutamide, enzalutamide – and then also that of radiation therapy directed to the primary. This is great but, having said that, what we don’t really know is should we combine these new treatments in older patients with metastatic disease? This is exactly the question the PEACE-1 phase III trial is asking.

Regarding the design of PEACE-1, PEACE-1 is a 2x2 phase III trial where patients are all receiving standard-of-care, and in the trial it was mostly ADT plus docetaxel. Then they were randomised to receive either standard of care alone, or standard of care plus abiraterone, standard of care plus radiation therapy directed to the primary site, or standard of care plus abiraterone plus radiation therapy. Again, here at ASCO, what we are reporting are the first data regarding the efficacy of abiraterone on top of standard of care with ADT plus docetaxel, again plus or minus radiation.

The median follow-up for this analysis is approximately 3.5 years. What we’ve found is that abiraterone very significantly improves the co-primary endpoint of radiographic progression-free survival. Actually, what we found was a reduction by half in the risk of radiographic progression or death. When it comes to medians what we saw was a median of two years for rPFS in the control arm with ADT plus docetaxel, and it was improved to four years and a half when abiraterone was added on top of ADT plus docetaxel. This means a two years and a half of additional radiographic progression-free survival for these men when they are receiving abiraterone on top of chemo-hormonal treatment, which is really big, of course, and very clinically meaningful.

This was supported by the other means of assessing PFS; for example, when looking at time to castration resistance it was more than doubled, favouring again abiraterone. Also, when we focused on symptomatic-defined progression-free survival we also saw a more than twice longer PFS favouring the abiraterone arm. Again, all the means of measuring PFS favoured abiraterone which was really fantastic.

In terms of safety, the news is also very reassuring. For example, the incidence of neutropenic fever for these men receiving ADT plus docetaxel was the same with or without abiraterone: 5% incidence in both arms. This also applied generally sticking to the haematological toxicity related to docetaxel. Some other side effects typical of docetaxel such as fatigue or GI toxicity were actually lower the abiraterone arm, maybe thanks to the co-prescription of prednisone. Regarding side effects of abiraterone, they were actually as expected, with an excess in hypertension, hypokalaemia, and transaminase increase, but it was actually modest. For example, regarding hypertension, the incidence was 12% in the abiraterone arm versus 8% in the control arm, so no big difference, to be honest.

I think we have clearly demonstrated that adding abiraterone to androgen deprivation therapy plus docetaxel very clearly improves radiographic progression-free survival and progression-free survival generally speaking. Given the magnitude of the benefit, I think this is already practice-changing – should we really, to be honest, deny two years and a half of good life without progression to all the patients? Honestly, I don’t think so, regardless of what the overall survival data will be in the future.

Regarding overall survival, I hope we can report data, perhaps right after the summer. We are actually currently conducting an overall survival sweep to try to collect the data and analyse them on time during the summer.

Generally speaking, we’ve been able to provide clear progresses to all the patients since 2015 and it becomes, of course, very important for all the patients to better understand how best to combine these new treatments, including chemotherapy, next generation hormonal agents, and radiation therapy. The data we are providing today with PEACE-1 are the very first regarding those questions. Actually, I think they’re really good, clearly in favour of combining right now ADT, docetaxel and abiraterone. We should have more data regarding the radiation therapy question in the future, perhaps in a year or two. Of course this will be very important, especially for men with oligometastatic disease, to better understand how best to combine local treatments with systemic intensified treatments.