Recent phase III evidence suggests a potential role for PARP inhibition in select patients with mHSPC harboring homologous recombination repair (HRR) gene alterations, particularly BRCA2. The AMPLITUDE trial106 was a randomized, double-blind, phase III study that enrolled 696 patients with newly diagnosed mHSPC and predefined HRR alterations, randomized to receive niraparib plus abiraterone versus placebo plus abiraterone, all in combination with ADT. In the overall HRR-altered population, the addition of niraparib significantly improved rPFS, with a 37% reduction in the risk of radiographic progression or death compared with abiraterone alone (HR=0.63; 95% CI: 0.49 to 0.80; p=0.0001). The magnitude of benefit was greatest among patients with BRCA1 or BRCA2 alterations, who comprised approximately 55% of the study population. In this subgroup, niraparib plus abiraterone was associated with a 48% reduction in the risk of radiographic progression (HR=0.52; 95% CI: 0.37 to 0.72; p<0.0001), largely driven by the BRCA2 subset. By contrast, benefit among patients with non-BRCA HRR alterations was uncertain and should be interpreted with caution. In an exploratory analysis of patients without BRCA1/2 alterations, the hazard ratio for radiographic progression-free survival (rPFS) was 0.81 (95% CI: 0.56 to 1.18). These data do not support routine extrapolation of benefit to non-BRCA HRR-altered patients. OS data from AMPLITUDE remains immature. While secondary endpoints, including time to symptomatic progression, favored the niraparib combination, longer follow-up is required to determine the impact on OS. Treatment with niraparib was associated with higher rates of adverse events, including higher rates of treatment discontinuation due to adverse events (14.7% versus 10.3%) and grade 3/4 toxicity (75.2% versus 58.9%), highlighting the importance of careful patient selection and toxicity monitoring. These findings represent the first phase III evidence evaluating PARP inhibitor use in the frontline metastatic hormone-sensitive setting and provide a rationale for incorporating PARP inhibition into treatment discussions for BRCA-positive patients.