Dr. Concepcion on Potential for Immunotherapy in CRPC

Raoul S. Concepcion, MD, FACS, director, Comprehensive Prostate Center, discusses the potential for immunotherapy in the treatment of patients with castration-resistant prostate cancer (CRPC).

Over the years, the CTLA-4 inhibitor ipilimumab (Yervoy) has been studied in patients with CRPC and has shown minimal efficacy as a single agent. Researchers know that metastatic CRPC tumors are “cold tumors,” meaning that they are not naturally immunogenic. However, recent data show that once men with metastatic CRPC progress through multiple lines of therapy, they will develop a tumor mutational burden or mutations as a result of treatment pressure selection. The 2 main genetic alterations that are associated with immunotherapy in CRPC are microsatellite instability-high and CDK12 biallelic loss.

Looking at these 2 groups of patients with MSI-H and CDK12 biallelic loss, investigators know that 8% of the former and 12% of the latter will respond to immunotherapy in the form of checkpoint inhibitors. There will be a place in the paradigm for immunotherapy, says Concepcion, but moving forward, it is going to be important for clinicians to know what testing to order to be able to detect these alterations in patients.