Pembrolizumab plus enzalutamide and androgen deprivation therapy in prostate cancer

As recently reported on Annals of Oncology, the KEYNOTE-991 trial investigating the addition of pembrolizumab to enzalutamide and androgen deprivation therapy in metastatic hormone-sensitive prostate cancer was stopped for futility.

The KEYNOTE-991 study is a placebo-controlled, double-blind, phase III trial involving 626 patients with metastatic hormone-sensitive prostate cancer to evaluate the efficacy and safety of adding pembrolizumab to enzalutamide and androgen deprivation therapy. Participants were randomly assigned to receive pembrolizumab 200 mg or placebo every 3 weeks, with oral enzalutamide and continuous androgen deprivation therapy. After a median follow-up of 21.1 months, radiographic progression-free survival and overall survival were not superior with pembrolizumab; more grade 3 or 4 adverse events occurred with pembrolizumab and any-grade rash was an additional safety signal (25.1% with pembrolizumab versus 9.3% with placebo). KEYNOTE-991 did not meet its primary endpoint and was stopped. «The results of this phase III KEYNOTE-991 study do not support the addition of pembrolizumab to enzalutamide and androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer due to a lack of superiority and increased frequency of high-grade adverse events. These results concur with recent results in metastatic castration-resistant prostate cancer studies and highlight the need for further work to identify the role of immune checkpoint inhibitors in the treatment of advanced prostate cancer», authors conclude.