Dr. Sartor: The next study from ESMO 2023 is a randomized, double-blind, phase III study called KEYNOTE-991. Now, this study was conducted in patients with metastatic hormone-sensitive prostate cancer. And they were randomized to receive ADT plus enzalutamide or ADT plus enzalutamide plus pembrolizumab. And, again, it was a blinded study.
No evidence of efficacy
The primary endpoint was RPFS, and they randomized 1251 patients; so, this is a large, randomized study. There was a prespecified interim analysis at 21 months, and the trial was terminated for futility. There was no evidence that there was value of pembrolizumab added to ADT and enzalutamide. And, in fact, the hazard ratio was slightly going the wrong way for the RPFS, although confidence intervals did overlap 1. In addition, a look at median overall survival indicated no evidence of benefit. There were higher rates of SAEs in the pembro arm. So, not only was there no evidence of efficacy, there was also higher toxicity in this setting.
KEYNOTE-991 was terminated by the sponsor for futility. The bottom line is, in unselected patients, there's no reason to consider giving pembrolizumab for patients with hormone-sensitive metastatic prostate cancer receiving ADT plus enzalutamide.