Enzalutamide Plus Androgen Deprivation Therapy in mCRPC

Researchers evaluated the immune effects of enzalutamide in patients with metastatic castration-resistant prostate cancer on androgen deprivation therapy (ADT). Presenting at the EMSO Congress 2022, lead author Ravi Madan reported that enzalutamide with ADT was associated with increased natural killer cells (NK) and myeloid-derived suppressor cells (MDSCs). The study also found that reduced interleukin (IL)-8 levels were associated with improved time to progression (TTP).

The authors compared their results with previous research on enzalutamide in biochemically recurring prostate cancer without ADT, wherein enzalutamide increased NKs but decreased MDSCs and did not impact IL-8 levels.

The study randomized 57 patients to receive enzalutamide monotherapy or enzalutamide plus PROSTVAC, a cancer vaccine targeting prostate-specific antigens (PSAs). Ten parental cell types (CD4+ and CD8+ T cells, T-regulatory cells, NK, NK-T cells, conventional and plasmacytoid dendritic cells, B cells, monocytes, and MDSCs) and 148 maturation/function subsets were evaluated in peripheral blood at baseline and at 1 month.

The full cohort had a median age of 57 years (range, 47-94) and a median PSA of 15.02 (range, 0.55-587), and both groups had a median TTP of 23.3 months. The researchers observed NK cells (P=.064) and MDSCs (P=.042) trended upward at 1 month versus baseline in all patients.

A total of 12 enzalutamide monotherapy and 12 enzalutamide plus PROSTVAC patients were assessed for immune effects. In the monotherapy group, increases in monocyte subsets and MDSCs were associated with reduced TTP. NK was also increased in the enzalutamide and PROSTVAC group (P=.064), and greater increases in PD-L1+ mature NK were associated with improved TTP. No associations with TTP were reported for T cells, B cells, or dendritic cells, the authors noted.

Given previously described associations between NK and better outcomes in prostate cancer and the increase in NK with enzalutamide observed in the study, the authors concluded their findings “could be important for developing new immunotherapy strategies in prostate cancer where PD1/PDL1 inhibition are not effective.”