Talazoparib (PARP inhibitor) + enzalutamide (AR inhibitor) boosts 3-year PFS to 77% in HRR-altered mHSPC

Talazoparib is an oral PARP1/2 inhibitor combined with enzalutamide, a potent androgen-receptor signaling inhibitor, on top of ADT in TALAPRO-3 (Phase 3, double-blind; NCT04821622) for metastatic androgen pathway modulation–sensitive prostate cancer with homologous recombination repair (HRR) gene alterations (n=599). At 3 years, investigator-assessed imaging-based PFS was 77% vs 56% with placebo + enzalutamide (HR 0.48, 95% CI 0.36–0.65; P<0.001), while interim 3-year OS was 78% vs 72% (HR 0.77, 95% CI 0.56–1.04; not yet significant); as a benchmark, enzalutamide + ADT already delivers strong rPFS benefit vs ADT alone in unselected mHSPC (ARCHES rPFS HR 0.39; median rPFS NR vs 19.0 mo), so TALAPRO-3 is effectively asking whether PARP adds incremental disease control on top of an established ARPI backbone in biomarker-selected patients. Toxicity clearly increased: serious AEs 42% vs 32%, grade ≥3 anemia 51% (notable “PARP-class” marrow suppression), and 2 treatment-related deaths—so the efficacy gain comes with substantial hematologic burden versus ARPI + ADT alone.