New Approval for the Nonmetastatic CRPC Population - Episode 2
Jorge Garcia, MD:The approval of darolutamide was based on a randomized phase III trial where patients with M0 CRPC [nonmetastatic castration-resistant prostate cancer]again, patients without evidence of radiographic progression with a suppressed testosterone level by guideline and with a rise in PSA [prostate-specific antigen]—were randomized in a 2:1 fashion to receive the standard, darolutamide, against a matching placebo twice a day. The primary endpoint of that ARAMIS trial was metastasis-free survival [MFS]. That was the primary endpoint for registration.
There were secondary endpoints that are quite important for us, such as survival, time to skeletal-related events, time to pain, time to PSA progression, and so forth. But really, the MFS has sort of become the gold standard for registration in that context. For patients who actually received darolutamide against those who received placebo, there was a significant delay in metastasis-free survivalalmost 22 months’ delay with a hazard ratio of 0.41, which basically is a 59% risk reduction of delaying metastases and/or dying from any cause.
The only caveat with the existing trials in the M0 space, and that includes the ARAMIS data, is the survival data still appear to be quite immature. So although we do believe MFS is a good surrogate marker for survival, the true survival data, statistically, have not been met for any of those 3 trials, including the ARAMIS data.
There are not a lot of differences between the trials in the M0 space when you look at ARAMIS, PROSPER, and SPARTAN. Although they’re 3 different trials, they really were aimed to identify the same patient population. There was a pre-stratification based upon your PSA doubling time, which is the logarithmic expression of how rapid your PSA rises over time; the presence or absence of bone health agents in those patients. But the reality of that is, when you look at the makeup of those patients, those patients were similar across all trials.
If you look, for instance, at unique differences, ARAMIS did require for you to have a minimum PSA, whereas, for instance, 1 of the other trials did not. Although it is apples to oranges when you look at these trials, because they haven’t been compared head-to-head, I think the makeup of these patients roughly appears to be the same.
Transcript edited for clarity.