Dr. Choudhury on Immunotherapy in Metastatic CRPC

Atish D. Choudhury, MD, PhD, co-director of the Prostate Cancer Center, senior physician, Dana-Farber Cancer Institute, and instructor in medicine, Harvard Medical School, discusses data with immunotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

Approximately 10% of unselected patients with mCRPC show evidence of a prostate-specific antigen (PSA) response to pembrolizumab (Keytruda) based on data from the phase II KEYNOTE-199 trial. It remains unclear who those patients are and whether they have a unique genomic signature that enriches for response, says Choudhury. Ongoing investigation is looking at optimal combination partners such as pembrolizumab and enzalutamide (Xtandi) as well as pembrolizumab and PARP inhibitors, he adds. Moreover, investigators are looking at whether there is a benefit to combining pembrolizumab with other immune checkpoint inhibitors and if that will show some increased activity compared with pembrolizumab alone.

At the 2019 Genitourinary Cancers Symposium, preliminary data showed encouraging activity in patients who received the combination of ipilimumab (Yervoy) and nivolumab (Opdivo). However, over 50% of patients discontinued therapy. Further studies will have to establish whether the benefit of the combination outweighs its toxicities. Interestingly, investigators noted an added signal of activity in patients with high tumor mutational burden (TMB) compared with what has been seen in patients with low TMB, concludes Choudhury.