The FDA approved talazoparib (Talzenna) in combination with enzalutamide (Xtandi) for adults with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer harboring homologous recombination repair (HRR) gene mutations. The approval covers mutations across a defined panel including BRCA1/2 and multiple other HRR genes and was based on the randomized TALAPRO-3 phase 3 trial in 599 patients. In the trial, the combination improved the primary endpoint of radiographic progression-free survival: median rPFS was not reached versus 45.8 months with placebo plus enzalutamide, with a hazard ratio of 0.48 (P<.0001). Overall survival data were immature at the time of analysis. The decision expands HRR-targeted treatment options for newly diagnosed metastatic HRR-mutated disease and reinforces the role of PARP inhibition in earlier lines for genetically defined prostate cancer.