Advances in Metastatic Castration-Sensitive Prostate Cancer - Episode 2
Neeraj Agarwal, MD:Until last year, we did not have much to treat our patients with for nonmetastatic castrate-resistant prostate cancer. This is a face of prostate cancer which is characterized by a rising PSA [prostate-specific antigen] level, and we know patients are toward onset of metastatic disease within a year or so. But really, we did not have much. All we were using were old-generation androgen receptor inhibitors, which are nonspecific. This has changed in the last year.
We started seeing the results of multiple, large clinical trials utilizing next-generation direct androgen receptor inhibitors that are very specific and stop the androgen receptors from driving the prostate cancer. These drugs include enzalutamide, apalutamide, and most recently darolutamide. All 3 trials, which are all registration trials, had more than 1000 patients in each trial. One trial had 1200 patients, and another trial had 1400 patients. The darolutamide trial had 1500 patients. And what we saw was dramatic.
These trials of these new drugs, which are novel drugs, compared against placebo. The primary endpoint for these trials was metastasis-free survival. The stage, which is painful, is a cause of death and suffering in our patients.
The primary endpoint was metastasis-free survival, meaning how long or how much of a difference there was in the onset of metastatic castrate-resistant prostate cancer. And as I said, there was a dramatic improvement or delaying of onset of metastasis compared with placebo, which was associated with a 16-month metastasis-free survival. In the patients who got enzalutamide, apalutamide, or darolutamide, there was almost a 2-year delay in the onset of metastasis. That was something that was profoundly affected.
There were even other endpoints, such as how much delay happened with the utilization of chemotherapy. As I mentioned, chemotherapy is not something our patients want to have. Another very important endpoint was, how much was a delay in chemotherapy? And that was also very significantly delayed by almost 2 years by these 3 drugs.
Again, very similar outcomes with these 3 agents. Patients who went on a trial had a rapidly rising PSA level. I really want to point this out. For trials with enzalutamide, such as the PROSPER trial, and with apalutamide, in the SPARTAN trial, and with darolutamide, with the ARAMIS trial, the inclusion criterion was a PSA doubling time of less than 10 months. But in reality, it was around 4 months.
These patients had rapidly PSA doubling times, and they were heading rapidly toward onset of metastases, the painful state of prostate cancer, and there was a very significant, very meaningful almost 2-year delay in the onset of metastasis. Given these results, apalutamide and enzalutamide have already been approved for the treatment of these patients who have nonmetastatic castrate-resistant prostate cancer. Based on the solid, meaningful and very dramatic improvement in metastasis-free survival, I do not have any doubt that we will have darolutamide available in our clinic very soon.
Transcript edited for clarity.