David Quinn, MD, Genitourinary Medical Oncologist, USC Norris Comprehensive Cancer Center, Los Angeles, California, discusses the clinical significance of the EORTC PEACE III clinical trial.

Transcript: 
Hi, I'm David Quinn. I'm a genitourinary medical oncologist at the University of Southern California Norris Comprehensive Cancer Center, where I'm also the Medical Director for the USC Norris Hospital and Clinics.
The EORTC PEACE III study looks at a number of endpoints with novel therapeutics. Here at ASCO 2019, we had an early presentation to address an important question.

As part of the study, patients are given enzalutamide and radium-223. Enzalutamide, an androgen receptor inhibitor, and radium 223, a radionuclide, a liquid radiation that homes in on bone metastases. These are both effective treatments for prostate cancer that extend overall survival.

The interest here extended from a prior study called ERA 223, where abiraterone, another hormonal agent, and radium were combined. We've previously had these data presented at ESMO 2018.

Somewhat surprisingly, an initial assessment of the combination of abiraterone and radium 223 showed an excess fracture risk, particularly early on therapy, and an excess death risk, which was of some concern, suggesting that the combination which made sense and we'd used but with more limited evidence.

From that perspective, there was pause. In ERA 223, the risk of early fractures was ameliorated by the use of antiresorptive agents, which are bisphosphonates or RANK ligand inhibitor, in that study, suggesting that there was an effect related to osteoporotic fractures. That was an interaction that was not expected between abiraterone and radium 223.

On further analysis, the risk of death did not pan out, once we followed the patients, which I think is encouraging. In PEACE III run by the EORTC, the question was raised as to whether there might be this similar interaction between enzalutamide and radium 223 with an excess early fracture risk.

In actual fact, when the ERA 223 data became available, the EORTC investigators modified their PEACE III study to include antiresorptive agents of one type or another, to mandate them, whereas prior to that amendment, it had been allowed but not required.

The result was that there was a very major increase in the number of metastatic prostate cancer patients getting these antiresorptive agents. What happened? The presentation here at ASCO showed that prior to the policy of requiring antiresorptive agents, there was actually a significant excess early fracture rate.

In addition, the EORTC investigators were able to provide good evidence that it didn't relate to cancer progression. It actually related to changes in the bone milieu with an equivalent of focal osteoporosis and fractures related to that.

This data from the PEACE III investigators from the EORTC addresses an important issue. It is practice changing. It confirms what we saw from ERA 223. In our practice, we need to give a RANK ligand inhibitor or a bisphosphonate to patients that are getting a second generation hormonal agent and radium 223.

It's also likely that we need to do it if we're just giving radium 223 alone. So this is important data and a great contribution from the EORTC.