Pembrolizumab Plus Enzalutamide for Patients With mCRPC

Research from Julie N. Graff, MD, and colleagues published in Prostate Cancer and Prostatic Diseases presented the results of cohorts 4 and 5 from the phase 2 KEYNOTE-199 study investigating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC).

Cohort 4 included patients with mCRPC who presented with Response Evaluation Criteria in Solid Tumors-measurable disease, while cohort 5 included those with bone-only or bone-predominant disease. Participants underwent treatment with pembrolizumab 200 mg every 3 weeks and enzalutamide until progression, unacceptable toxicity, or withdrawal.

The study’s primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), overall survival (OS), and safety.

Across the cohorts, 126 patients received pembrolizumab plus enzalutamide, with 81 patients in cohort 4 and 45 in cohort 5. The median age of the participants was 72 years, and 87.3% had undergone 6 months or more of enzalutamide treatment prior to the study’s start.

For patients in cohort 4, the ORR was 12.3% (95% CI, 6.1-21.5), while the mediation duration of response was 8.1 months. Five patients demonstrated an objective response of 6 months or longer.

DCR was 53.1% (95% CI, 41.7-64.3) in cohort 4 and 51.1% (95% CI, 35.8-66.3) in cohort 5. The median OS rate was 17.6 months (95% CI, 14.0-22.6) and 20.8 months (95% CI, 14.1-28.9) in cohorts 4 and 5, respectively.

Dr. Graff and colleagues reported that 35 (27.8%) patients had grade 3 or higher adverse events (AEs), while 2 patients in cohort 4 died due to immune-related AEs.

“The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile,” the researchers wrote.