Dr. Sartor: Another interesting trial at ESMO 2023 was the ENZA-p trial. Now, this was conducted in metastatic CRPC patients, all of whom were PSMA PET–positive, and the randomization was either to enzalutamide at a standard dose of 160 mg or to enzalutamide plus an adaptive dosing of PSMA lutetium.
First of all, let me explain a little bit about what adaptive dosing actually is. So, rather than giving consecutive doses, in this case, there were four planned doses of the PSMA lutetium; for patients who had received the lutetium, there was a second PSMA PET scan performed after two cycles. If the disease had gone away, then no more lutetium was given. On the other hand, if the disease was still present, then PSMA lutetium for up to four doses was given. So, in other words, some of the patients only received two doses and some received four.
Now, this was an Australian trial. The primary endpoint was PSA progression–free survival, and they had a variety of other secondary endpoints, including radiographic PFS, PSA 50%, and PSA 90%. Okay, what did they find?
Progression–free survival outcomes
The median follow-up in this study was about 20 months for 162 patients randomized, and, without a doubt, the PSA progression–free survival was longer with the combination therapy, as opposed to enzalutamide alone — about 13 versus 17.8 months. The PSA 50 response rate was higher for the combination, and, actually, 93% of the patients on the enzalutamide plus lutetium arm had a 50% decline in their PSA. And that, I think, is quite striking; as is the 68% of the patients in the combination arm who had a PSA decline of 90% or more. That was substantially better than what was seen in the control group.
The RPFS, unfortunately, was not particularly well-measured, and I'll simply say that that was a consequence of the Australians utilizing the PSMA PET scan to call progression instead of conventional imaging. So, the RPFS was not quite analyzable. It trended better, but it wasn’t quite analyzable in my mind.
Similar rates of serious adverse events
With regard to the serious adverse events, basically the rate was the same between the two arms, 33% and 35%. Adaptive dosing was utilized in a minority of patients; but, nevertheless, these patients could demonstrate that just receiving two doses and stopping could be appropriate for those with dramatic PSMA PET responses.
All in all, this is not a practice-changing study. It's a phase II trial. But it's a provocative study showing that PSMA lutetium, given in combination with enzalutamide, is better than enzalutamide alone for CRPC patients with a positive PSMA PET scan for metastatic disease, according to the criteria at use. And the treatment is well-tolerated. Interesting study, and we look more for these types of studies in combination to proceed in the years ahead.