Transcript: Alicia Morgans, MD, MPH: The PROSPER trial is a phase III international study of patients with nonmetastatic CRPC [castration-resistant prostate cancer]. These patients had high-risk disease because we identified them by having a PSA [prostate-specific antigen] doubling time of less than or equal to 10 months. On standard imaging, a bone scan and a CT [computed tomography] scan of the abdomen and pelvis didn’t have evidence of metastatic disease. All patients were enrolled and randomized to treatment with either ADT [androgen deprivation therapy] and a placebo or ADT and enzalutamide at standard doses. The primary end point of this trial was metastasis-free survival [MFS], which is actually a novel end point created for these trials of nonmetastatic CRPC. This end point encompassed progression with metastatic disease or death from any cause. In the trial, we saw that treatment with ADT plus enzalutamide was actually associated with a significantly longer metastasis-free survival than treatment with ADT and placebo—about 22 months.
When I think about the implications of PROSPER or any of these trials, I’m really struck by the fact that we’re delaying the time to patients developing metastatic disease. This is a clinically meaningful end point because patients can develop pain, fatigue, and anxiety related to the development of metastases. Certainly, the FDA also thought that this was an appropriately long period of prolongation of metastasis-free survival, and it has given us the indications and the approval for use of these drugs in prolonging metastasis-free survival in nonmetastatic CRPC.
Elizabeth Heath, MD: The darolutamide trial is really looking at over 1500 men and in a 2:1 randomization to either get darolutamide or placebo. It’s very much in line with the other 2 trials, and it’s looking at a patient group for which the PSA doubling time is less than 10 months. I think that is sort of the critical piece for all 3 trials. But it’s nice that they all kind of look at the same patient group. You know, a little more aggressive because not all nonmetastatic castration-resistant patients are the same. Some are going to plod through. You may not want to do much for these guys because they’re really not symptomatic. No one is that worried. But when it starts to pick up the speed and the PSA is really starting to take off, less than 10 months has really been shown to be that magical point. I think all the other trials have supported that sort of patient group.
Then there’s the stratification of patients. Here, they actually tried to figure out less than 6 months versus over 6 months in terms of the doubling time. So it’s very consistent with the other trials. I think the results are completely unsurprising, but you can’t take it for granted. You never know that all the agents will come up with the same type of results. But in terms of the metastasis-free survival, which is the primary end point, it is consistent with the other data set. So it was much better than placebo.
Transcript Edited for Clarity