Discussion
TALAPRO-2, death, tumor HRR
In one of the largest studies in patients with mCRPC with HRR gene alterations, the prospectively defined, alpha-controlled primary outcome in the combined HRR-deficient population showed that talazoparib plus enzalutamide resulted in a clinically meaningful and statistically significant 55% reduction in risk of progression or death versus placebo plus enzalutamide as first-line treatment. These results build on the previous subgroup analysis of the HRR-deficient patients in the all-comers cohort, which showed a 54% reduction in risk of progression or death for talazoparib plus enzalutamide versus placebo plus enzalutamide (HR, 0.46; 95% CI, 0.30 to 0.70; Importantly, TALAPRO-2 was not enriched for patients with Two other recent phase 3 trials have explored the combination of PARP inhibitors and the androgen biosynthesis inhibitor abiraterone acetate/prednisone as first-line treatment for mCRPC. The PROpel (The main limitations of this study are due to the rapidly changing treatment landscape for patients with mCRPC. For example, the use of PARP inhibitors as a subsequent therapy was limited to a small number of patients (3 in the talazoparib group and 18 in the placebo group; all received olaparib). This small number most likely reflects the limited availability of PARP inhibitors for the treatment of mCRPC when the TALAPRO-2 study was carried out. Based on established phase 3 dataThe safety profile of talazoparib plus enzalutamide was closely aligned with that observed in the previously reported all-comers populationIn conclusion, these results support the use of talazoparib plus enzalutamide as a potential first-line treatment option for patients with mCRPC harboring tumor HRR gene alterations.