Apalutamide and the TITAN Clinical Trial

Neeraj Agarwal, MD:TITAN was a phase III registration trial of patients who had castration-sensitive metastatic prostate cancer. As we know, apalutamide is a direct, specific androgen receptor inhibitor. In this trial, more than 1000 patients were randomized to standard-of-care therapy, which included chemotherapy. If patients wanted to get chemotherapy, they were allowed to get chemotherapy. Basically, all patients who had any form of castration-sensitive metastatic prostate cancer, whether they had low-volume or high-volume disease, whether they had visceral metastases or not. And it did not really matter what their Gleason score was.

Anyone with castration-sensitive metastatic prostate cancer were eligible for this trial. They were randomized to standard-of-care therapy with androgen suppression therapy versus androgen suppression therapy with apalutamide. As I said, prior receipt of chemotherapy at the onset of metastatic castration-sensitive prostate cancer was allowed. And what we saw was really dramatic. There was a 33% reduction in risk of death.

The trial had dual endpoints, or 2 endpoints: overall survival and radiographic progression-free survival. This trial is unique from other trials in the sense that it had dual primary endpoints of overall survival and radiographic progression-free survival, and both were met at the time of first interim analysis—after a follow-up of only 22 months. So this was another example of how good the drug is.

There was a 33% risk reduction. As far as overall survival was concerned, in patients who received apalutamide, there was a 33% reduction in risk of death. Regarding radiographic progression-free survival, there was a 52% reduction in risk of progression or death.

With these primary endpoints being met at the time of first interim analysis, this basically tells us the drug is very effective, and we are really hoping that it will lead to the approval and availability of this drug for our patients in the very near future. And we are talking about a few months.

I’d like to point out 1 more thing about the TITAN study. We always talk about adverse effects, and how our patients feel when they get these newer drugs. Looking at the adverse-effect profile, if you look at grade 3 or 4 adverse effects, which are clinically meaningful, there really was no difference in the grade 3 or 4 events. They were 40% in the control arm and 42% in the experimental arm or in the apalutamide arm. So we are really not impacting quality of life. We are actually preserving quality of life while we’re increasing survival in a very meaningful fashion.

Transcript edited for clarity.