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 decision follows results from the randomized, double-blind, placebo-controlled TALAPRO-3 phase 3 trial. TALAPRO-3 enrolled 599 patients with HRR-mutated mAPMN/S prostate cancer and compared daily enzalutamide plus talazoparib versus enzalutamide plus placebo. Regulators based the primary efficacy endpoint on investigator-assessed radiographic progression-free survival (rPFS) using RECIST 1.1 and PCWG3 criteria. Median rPFS was not reached in the talazoparib arm versus 45.8 months in the placebo arm (HR 0.48; 95% CI 0.36–0.65; P<.0001). Overall survival data were immature at the time of the rPFS analysis, but the approval expands treatment options for a patient group facing aggressive disease and limited choices. Eligible HRR alterations included mutations in ATM, ATR, BRCA1/2, and several others, determined prospectively using tumor tissue or circulating tumor DNA next-generation sequencing assays.