Immune Checkpoint Inhibitors in Prostate Cancer

SIMPLE SUMMARY: Metastatic prostate cancer is an incurable disease with limited treatment options. Immunotherapy has demonstrated significant success in multiple cancer types but efforts to harness its benefit in prostate cancer have so far largely been unsuccessful. In this review, we analyze the preclinical rationale for the use of immunotherapy and underlying barriers preventing responses to it. We summarize clinical studies evaluating checkpoint inhibitors in prostate cancer. In the end, we review ongoing trials exploring combination immune checkpoint inhibitors in combination with other agents with the intent to modulate the immune system to improve treatment outcomes. ABSTRACT: Metastatic prostate cancer is a lethal disease with limited treatment options. Immune checkpoint inhibitors have dramatically changed the treatment landscape of multiple cancer types but have met with limited success in prostate cancer. In this review, we discuss the preclinical studies providing the rationale for the use of immunotherapy in prostate cancer and underlying biological barriers inhibiting their activity. We discuss the predictors of response to immunotherapy in prostate cancer. We summarize studies evaluating immune checkpoint inhibitors either as a single agent or in combination with other checkpoint inhibitors or with other agents such as inhibitors of androgen axis, poly ADP-ribose polymerase (PARP), radium-223, radiotherapy, cryotherapy, tumor vaccines, chemotherapy, tyrosine kinase inhibitors, and granulocyte-macrophage colony-stimulating factor. We thereafter review future directions including the combination of immune checkpoint blockade with inhibitors of adenosine axis, bispecific T cell engagers, PSMA directed therapies, adoptive T-cell therapy, and multiple other miscellaneous agents.