Pembrolizumab for metastatic castration-resistant prostate cancer: trials and tribulations

Pembrolizumab has not benefitted unselected metastatic prostate cancer patients when combined with chemotherapy, next-generation hormonal agents (NHA), or poly(ADP-ribose) polymerase inhibitors (PARPi). PD-L1 positivity does not predict the response to pembrolizumab in this disease. A small number of responding patients can likely be explained by rare genetic and molecular defects, and more innovative combination strategies are needed to improve outcomes in prostate cancer patients who are not sensitive to pembrolizumab. Emphasis should be placed on developing additional or alternative immuno-oncology approaches beyond classical immune checkpoint inhibition.