Programmed cell death 1 (PD-1) inhibitors have shown anti-tumor activity in patients with melanoma, renal cell, non-small cell lung cancer, and bladder cancer. However, patients with castration-resistant prostate cancer demonstrated no response to such immunotherapies in past studies. Now, a research team led by Julie Graff, M.D., assistant professor and oncologist with the Knight Cancer Institute, has shown clear evidence of meaningful clinical activity for PD-1 blockade in men with metastatic prostate cancer resistant to androgen deprivation.
The team’s paper, published on July 13 in Oncotarget, outlines the study involving 10 men with metastatic prostate cancer who were treated with pembrolizumab, a monoclonal antibody that binds to the PD-1 receptor. Three of the first 10 participants enrolled in the ongoing clinical trial experienced rapid reductions in prostate specific antigen, or PSA, an early measure of treatment effect. The participants who responded to PD-1 blockade started with serum PSA levels of 46, 71 and 2,503 ng/ml. These PSA levels plummeted to less than 0.1 ng/ml after treatment, and these three patients remain free of progression at 30, 55 and 16 weeks of follow-up, respectively.
“It’s pretty remarkable, especially in light of the fact that many people doubted this approach could work at all,” said Graff. “You don’t get responses like this with almost any other treatment.” The study’s authors note these results are preliminary but the surprising and robust responses seen in this study warrant to re-examination of PD-1 inhibition in prostate cancer. Future studies are in the planning stages.
Read the full press release here.
In addition to lead author Graff, the following OHSU investigators contributed to this study: Joshi Alumkal, M.D., George Thomas, M.D., Jeremy Cetnar, M.D., M.S.H.P.R., Frederick Ey, M.D., F.A.C.P., Raymond Bergan, M.D., Rachel Slottke, and Tomasz Beer, M.D., F.A.C.P. Additional authors include researchers from the VA Portland Health Care System, Johns Hopkins University School of Medicine and the Providence Portland Medical Center.
Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. Funds from the Bloomberg Kimmel Institute supported a portion of the laboratory work.