Biomarkers for Programmed Death‐1 Inhibition in Prostate Cancer

AbstractProstate cancer is the second leading cause of cancer death in American men. Despite the common nature of this disease, there is a poor understanding of biomarkers that predict responsiveness to immunotherapeutic agents such as the programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) inhibitors. Herein we describe a case of complete remission with pembrolizumab therapy in a metastatic castrate‐resistant prostate cancer patient with a complex germline MSH2 alteration (Boland inversion) in association with a tumor demonstrating high microsatellite instability. Potential utility of high mutational burden assessed by an experimental circulating tumor DNA assay is also shown. The literature concerning biomarkers for PD‐1 inhibition is reviewed, including data for various mismatch repair gene deficiencies, microsatellite instability, tumor mutational burden, PD‐L1 3' untranslated region mutations, selected POLE mutations, and biallelic CDK12 mutations. Taken together, although prostate cancer is generally believed to be a tumor unresponsive to PD‐1 inhibition, careful dissection of tumor biology is able to provide an approach toward predictive biomarkers that has the potential for expanded clinical utility.Key Points. Biomarkers for anti‐PD1 and anti‐PDL1 therapy are poorly defined in prostate cancer.Recent advances are defining new important classes of responsive patients.

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