DR DREICER: So that was a small Phase II exploratory study that Dan George at Duke led. It was in nonmetastatic patients, only PSA, using a relatively low dose of orteronel, 300 milligrams BID without steroids.
Bottom line is: There was some activity, as one would have anticipated. It was relatively well tolerated. Only 2 of 39 patients actually needed to go on steroids for a mineralocorticoid-related toxicity. So what it established is a proof of concept that one can do such a trial in nonmetastatic PSA-only disease.
DR LOVE: What is the explanation for why you can get away without the steroids? And what kinds of clinical symptomatology or lab work do you look for to start it?
DR DREICER: Orteronel versus abi impacts on the 2 enzymes, the 17 hydroxy and the 17 lyase somewhat differently, so it spares mineralocorticoid toxicity a bit. In the Phase I development of the compound, there were relatively large cohorts treated without steroids. The pharma company developing the compound opted not to take the nonsteroid-requiring dose into Phase III.
So the Phase III trials, which are just about complete in terms of accrual, very similar to the abiraterone trials of pre- and postchemotherapy, involve a dose of orteronel with steroid. So that was a decision that was made.
DR LOVE: Where do you see this agent heading?
DR DREICER: When you develop a compound, in a sense, that mirrors another compound without any other theoretical advantages other than perhaps being able to be used without steroids but you don’t take advantage of that, it’s strikingly difficult to see other than a price issue, et cetera, unless it’s head to head compared.
DR SMITH: I agree with the point she made. I would like to add, though, that there is a very important Phase III trial of orteronel that is at a dose that does not require steroids. It’s an RTOG trial looking at men with high-risk disease, androgen deprivation therapy plus radiation with or without orteronel, important for several reasons. First, it’ll systematically look at the question of requirement of steroids with orteronel, and then it’ll ask a very important question about the role of earlier CYP17A inhibition in prostate cancer.
DR DREICER: I agree, although, as you know, it will not be a registration trial. And, therefore, the use of the drug in more of the larger population of patients will be driven by the registration trial.