Pembrolizumab in mCRPC – Combination therapies as breakthrough to success?

Immune checkpoint inhibitors (ICIs) have shown promising antitumor activity in various malignant diseases. This narrative review provides an update on ongoing clinical studies investigating the only FDA-approved ICI programmed death receptor 1 (PD-1) inhibitor pembrolizumab in mono- and combination therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).Although most clinical trials investigating pembrolizumab as mono- or combinational therapy did not meet their primary endpoints, there exist subgroups of patients that demonstrate impressive responses rates justifying further investigation of ICI in prostate cancer. Beside combination of pembrolizumab with approved mCRPC agents, innovative approaches, like combining pembrolizumab with radioligands, deoxyribonucleic acid vaccines or innovative immunotherapeutic agents (i.e., ONC-392, AMG160, BXCL701) are ongoing exerting promising preliminary findings.ICI monotherapy seems to be effective in a small biomarker-preselected population, however, there is evidence that especially novel ICI combination approaches can improve patient survival, which could ultimately refocus and revolutionize the treatment of mCRPC.