At the recent European Society for Medical Oncology meeting, OHSU oncologist Julie Graff, M.D., presented the first evidence of meaningful clinical activity for PD-1 blockade in men with aggressive, advanced-stage prostate cancer. It’s a heartening result given that prior studies of men with metastatic prostate cancer showed no evidence of anti-tumor activity with immune therapies that work by blocking PD-1 signals. In a video interview with ecancertv.org, Graff talked about what the findings could mean for patients.
Graff and colleagues enlisted 27 men with metastatic prostate cancer resistant to androgen deprivation therapy and the androgen receptor antagonist enzalutamide. They treated the men with pembrolizumab, a monoclonal antibody that binds to the PD-1 receptor. Five of the 27 showed a strong response to the treatment. Their PSA levels dropped by 99 percent and the tumors that could be measured shrank substantially.
“I’m hopeful that in the future we’ll find a select group of men whose cancers are curable or at least can have profound responses on this type of therapy,” says Graff, an oncologist specializing in prostate cancer at the OHSU Knight Cancer Institute.
‘If we understand why it works in some patients maybe we can prime other patients so that they can become responders too’
Important questions remain unanswered: Can PD-1 blockade can improve survival in men with metastatic, castration-resistant prostate cancer? Will it be possible to select which patients are likely to respond to the treatment? The ongoing phase II study at the Knight Cancer Institute should provide more evidence about the potential benefits.
Graff and colleagues plan to enroll about 15 more subjects in the trial and try to obtain biopsies from the new participants to explore the biology of cancers that respond to the therapy. They hope to find characteristics that can predict which patients are most likely to respond.
“If we understand why it works in some patients maybe we can prime other patients so that they can become responders too,” Graff says. “But I’ll bet even now in 2016 there’s quite a few men around the world who can benefit from this type of medication. We just need to figure out who they are.”
Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer by Julie N. Graff, Joshi J. Alumkal, Charles G. Drake, George V. Thomas, William L. Redmond, Mohammad Farhad, Jeremy Cetnar, Frederick S. Ey, Raymond C. Bergan, Rachel Slottke and Tomasz M. Beer, Oncotarget (2016)
This research was funded by Merck Sharp & Dohme Corporation, and funds from the Bloomberg Kimmel Institute supported a portion of the laboratory work.