Medicine Matters oncology

Here at ASCO 2021, we're presenting the very first results of the PEACE-1 phase III trial in men with de novo metastatic prostate cancer. As you are probably all aware of, we've been treating men with metastatic prostate cancer with androgen deprivation therapy alone for decades until 2015, when docetaxel and the next generation of hormonal agents, as well as local radiation therapy, became standard thanks to findings from randomized trials. What we don't really know at the moment is how to best combine these new treatments together with standard of care with ADT in these men, and this is actually exactly the question PEACE-1 is asking-- how to best combine.

So the design of the trial is as follows. Men are treated with standard of care, and the standard of care consisted initially in androgen deprivation therapy alone. And then, rapidly, starting in 2015-16, men received docetaxel as well in their standard of care and there were randomized between standard of care alone, or together with abiraterone, or together with radiation therapy directed to the prostate, or together with abiraterone and radiation.

Here at ASCO, we are focusing on the very first data from the trial-- namely, that of radiographic progression-free survival, which is one of the two co-primary endpoints with overall survival, regarding the question of abiraterone in this two-by-two design phase III trial. What we found was that indeed, for men receiving castration plus docetaxel as the standard of care, abiraterone tremendously improved radiographic progression-free survival, with medians being two years in the control arm with ADT plus docetaxel and four years and a half in men receiving abiraterone on top of ADT plus docetaxel-- so an absolute difference of two years and 1/2, believe it or not. And that's a reduction of 1/2 regarding the risk of progressive disease or death in these men.

This data on RPFS was actually confirmed and corroborated by findings looking at other means at looking at PFS, such as time to castration-resistant, or also symptomatic-defined PFS. All these endpoints were clearly improved with abiraterone, with medians being very similar as compared to the one I just mentioned.

What is the price to pay, from a patient perspective, in terms of toxicity? Here again, we have some good news. And actually, the incidence of neutropenic fever related to docetaxel was exactly the same in the two arms, 5% with and 5% without abiraterone. Also, some other docetaxel side effects, such as fatigue or GI toxicity, were actually reduced in the abiraterone arm, perhaps thanks to the prednisone. And finally, regarding the side effects related to abiraterone, such as hyperkalemia, hypertension, or transaminase increase, it was exactly as expected-- so just a minimum difference between the two arms.

So with all this, we're waiting for the overall survival data. Hopefully, we will have this later on this year. But even before we have the OS data, I think there's three questions-- whether using ADT plus docetaxel plus abiraterone should just become a new standard of care for these men, given that they will enjoy an additional two years and a half of RPFS defined with a strong measure, which is imaging, not just subjective one, from the doctor. And I think this is very important to patients. We should probably not deny them this benefit. Another argument being that abiraterone is becoming standard-- not only standard of care, but also a generic drug in many, many countries.

Regarding next steps, not only we will soon have the overall survival data regarding the abiraterone question-- and I hope that we can release this data before the end of the year-- but also, PEACE-1 will answer some other questions. For example, does this apply does this data apply-- for men with neuroendocrine differentiation from their adenocarcinoma? We don't really know. Also, how best to combine local radiation therapy together with the systemic treatments for these men with metastatic disease? Again, PEACE-1 will address this question.

Another big question I would love to know the answer of is whether abiraterone increases the risk of osteoporosis, for example. And this will be also measured in PEACE-1. And actually, PEACE-1 will address many other questions. So I'm looking forward to these answers, again starting later on this year, and then in the coming years.