Road to PROSPERity.

Top Line: Enzalutamide and the PROSPER trial are back in the spotlight for non-metastatic, castration-resistant prostate cancer (CRPC).

The Study: Why? Mature overall survival results. If you can even remember life way back before 2020, the initial results of PROSPER showed an almost 2-year improvement in metastasis-free survival. Recall, men in PROSPER had a PSA doubling time ≤10 months on ADT with no baseline mets on conventional imaging. In the overall survival analysis, the addition of enzalutamide to ADT reduced relative risk of death by 27% and prolonged median survival from 56 to 67 months. The rate of prostate cancer death was 19% with ADT + enzalutamide compared to 29% with ADT alone. However the rate of non-prostate cancer death was 12% compared to 9%, perhaps due to the increase in major cardiovascular events with the former. Indeed, the most common adverse event leading to death was cardiac, and most of those events happened in men with pre-existing cardiovascular disease. This all adds to the ongoing debate over the cardiovascular tradeoffs of different forms of androgen blockade.

TBL: Starting enzalutamide in men with localized CRPC and a PSADT of ≤10 months  extends survival by almost one year. | Sternberg, N Engl J Med 2020