Counting the loot.

Top Line: Three androgen receptor antagonists (enzalutamide, apalutamide, and darolutamide) are available for men with non-metastatic, castration resistant prostate cancer (nmCRPC).

The Study: All three improved metastasis-free survival, and now we have final survival results showing that all three improve overall survival compared to continuing first-line ADT alone. Survival outcomes from ARAMIS, the phase 3 darolutamide trial, were initially reported at ASCO 2020 and are now available in the full publication. At 3 years, darolutamide improved overall survival rate from 77 → 83% with a 31% relative reduction in death. So, which AR antagonist is preferred? The current arguments for or against certain drugs centers around toxicity. The problem is another study at ASCO 2020 demonstrated major discrepancies in the rates of adverse events on the placebo arms of these trials, concluding adverse event reporting in both PROSPER and ARAMIS were less precise than those of SPARTAN.

TBL: Darolutamide joins enzalutamide and apalutamide in improving overall survival for men with nmCRPC, but caution should be exercised in directly comparing trial data to decide which drug to use. | Fizazi, N Engl J Med 2020