Immunotherapy with Keytruda (pembrolizumab) may be an effective way to treat advanced-stage prostate cancer, according to a preliminary study conducted by researchers at Oregon Health and Science University (OSHU) Knight Cancer Institute.
Graff is the senior author of the study “Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer,” published in the journal Oncotarget.
Keytruda is a monoclonal antibody that blocks the PD-1 receptor on the surface of immune T-cells, allowing them to recognize and destroy tumor cells. The FDA-approved drug has been shown to work well in melanoma and lung cancer but had so far not produced any evidence of anti-tumor activity in prostate cancer.
Researchers administered Keytruda in 10 men with metastatic prostate cancer who had received androgen deprivation therapy or the androgen receptor antagonist Xtandi (enzalutamide) but failed to respond to it.
Three of the 10 men who participated to the trial responded remarkably well to Keytruda treatment. Prostate specific antigens (PSA) in their blood, which is an early measure of treatment response, dropped rapidly and dramatically (from 46, 71, and 2,503 ng/ml respectively, to less than 0.1 ng/ml).
In addition, two of the three men saw their tumors shrink and reported a reduction in cancer-related pain to the point of not needing their opiate pain medication. Finally, the three patients who responded to Keytruda remained free of cancer progression at 30, 55, and 16 weeks of follow-up, respectively.
Drugs currently available to treat prostate cancer rarely result in PSA levels lower than 0.2 ng/ml. “You don’t get responses like this with almost any other treatment,” Graff said.
It is still unclear why only three of the 10 men who participated in the clinical trial responded to treatment with Keytruda, while others showed no signs of clinical benefit. It is not yet possible to conclude that blocking PD-1 signaling can improve survival in men with metastatic prostate cancer, or to predict which patients will respond to treatment.
More research is needed to better understand the mechanisms by which Keytruda reduces prostate cancer and which factors may influence the therapeutic effect of the drug. The team is continuing to monitor the patients enrolled in the clinical trial and have recruited more participants. Future studies are also being planned.