Antonarakis ES, Piulats JM, Gross-Goupil M, et al. - Researchers investigated the antitumor activity and safety of pembrolizumab in three parallel cohorts of a larger metastatic castration-resistant prostate cancer (mCRPC) population. Three cohorts of patients (n = 258) with mCRPC treated with docetaxel and one or more targeted endocrine therapies were assessed in phase 2 KEYNOTE-199 study; 133 in cohort 1, 66 in cohort 2, and 59 in cohort 3. Patients with RECIST-measurable programmed death ligand 1 (PD-L1)–positive and PD-L1–negative disease, respectively, formed cohorts 1 and 2. Patients with bone-predominant disease, regardless of PD-L1 expression formed cohort 3. Outcomes revealed that a subset of patients with RECIST-measurable and bone-predominant mCRPC previously treated with docetaxel and targeted endocrine therapy exhibited antitumor activity in correlation to receiving pembrolizumab monotherapy with an acceptable safety profile of the drug. Witnessed responses appear durable, and overall survival estimates are encouraging.