(UroToday.com) Pembrolizumab, an anti-PD-1 antibody, has antitumor activity as monotherapy in patients with heavily pre-treated, PD-L1 positive advanced prostate cancer as well as mCRPC patients regardless of PD-L1 expression status. KEYNOTE-365 is a 4-cohort study evaluating the combination of pembrolizumab in combination with multiple agents, as shown below. Results from Cohort B, the combination of pembrolizumab with docetaxel and prednisone, were previously presented at ESMO 2020 after a median follow-up of 20 months. In this presentation, Dr. Appleman shared updated data with a median time of follow-up of 32.4 months. The study schema is shown below.
In total, 104 patients were treated in cohort B, and 2 patients still have ongoing treatment. The primary reason for treatment discontinuation was disease progression. Patient characteristics are shown in the table below
Overall, 74% of patients experienced some PSA response from baseline, and 34% of patients had a confirmed PSA response of greater than 50%. The overall response rate in patients with measureable disease (52 patients) was 23.1%, and 73.1% of patients experienced disease control on treatment. There were no complete responses, 12 partial responses, and 26 stable disease patients of any duration. Over 90% of patients had some tumor reduction from baseline. The rPFS of the cohort was 8.5 months, with an overall survival of 20.2 months. 
With regards to safety, treatment-related adverse events are shown in the table below. Over a third of patients had any immune-mediated adverse event, with the most common grade 3 or higher events being pneumonitis and colitis. Two patients died from treatment-related pneumonitis. 
Dr. Appleman concluded this longer follow-up data showed antitumor activity with the combination of pembrolizumab and docetaxel with prednisone, specifically a 34% confirmed
PSA response rate and 23.1% ORR. The KEYNOTE-921 randomized phase 3 study of docetaxel and prednisone with or without pembrolizumab in patients previously treated with abiraterone or enzalutamide is currently enrolling (NCT03834506).
Presented by: Leonard Appleman, MD, Ph.D., University of Pittsburgh Medical Center
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021