The FDA approved talazoparib (Talzenna) in combination with enzalutamide (Xtandi) for adults with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer harboring HRR gene mutations. The decision is based on TALAPRO-3, a randomized, double-blind, placebo-controlled Phase 3 trial enrolling 599 patients. In the study, the talazoparib-enzalutamide arm achieved a statistically significant improvement in radiographic progression-free survival. Investigators reported median rPFS was not reached with the combination versus 45.8 months with placebo plus enzalutamide, with an HR of 0.48 and p<0.0001. Overall survival data remained immature at the time of the primary analysis. The approval expands PARP inhibitor use in newly diagnosed metastatic settings with prospectively identified HRR mutations and underscores how genomic stratification continues to reshape standard-of-care sequencing in prostate cancer.