The FDA approved talazoparib (Talzenna) in combination with enzalutamide (Xtandi) for adults with metastatic hormone sensitive prostate cancer carrying homologous recombination repair (HRR) gene mutations. The approval covers patients with HRR mutations including ATM, ATR, BRCA1, BRCA2, PALB2 and others, with eligibility determined prospectively via tumor tissue or circulating tumor DNA-based next-generation sequencing. The decision was based on results from the randomized, double-blind, placebo-controlled TALAPRO-3 trial. In 599 patients, the primary endpoint—investigator-assessed radiographic progression-free survival—was not reached in the talazoparib-plus-enzalutamide arm versus 45.8 months in the placebo arm (hazard ratio 0.48; P<.0001), with overall survival data immature at the time of analysis. Regulators cited consistent benefit across BRCA and non-BRCA HRR mutations. The approval gives a new combination option for patients with newly diagnosed mHSPC with HRR gene alterations, a group facing aggressive disease and limited treatment choices.