The final overall survival (OS) results from the Phase 3 TALAPRO-2 trial were presented at ASCO GU 2025, highlighting the efficacy of talazoparib, a PARP inhibitor, in combination with enzalutamide as a first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) gene alterations. The study demonstrated significant survival benefits, particularly for patients with BRCA1/2 mutations, while also exploring outcomes for those with non-BRCA HRR alterations.

Study Overview

TALAPRO-2 was a randomized, placebo-controlled trial evaluating the combination of talazoparib and enzalutamide compared to enzalutamide alone in patients with HRR-deficient mCRPC. The final OS analysis confirms the treatment’s efficacy, complementing earlier findings on radiographic progression-free survival (rPFS) and safety.

Overall Survival (OS) and Radiographic Progression-Free Survival (rPFS)

• OS Benefit: Patients receiving talazoparib plus enzalutamide had a median OS of 45.1 months compared to 31.1 months for the enzalutamide-only group (Hazard Ratio [HR]: 0.622, 95% Confidence Interval [CI]: 0.475–0.814).
• rPFS: The combination therapy significantly prolonged rPFS, with a median of 30.7 months, compared to 12.3 months in the placebo group (HR: 0.468, 95% CI: 0.359–0.612).

Stratified Analysis by HRR Gene Mutation Type

The study further analyzed the efficacy of the treatment based on HRR mutation subtypes, revealing distinct benefits among different genetic subgroups:

BRCA1/2-Positive Patients

• The most pronounced OS benefit was observed in patients with BRCA1/2 mutations.
• Median OS was not reached in the talazoparib + enzalutamide group, compared to 28.5 months in the placebo + enzalutamide group.

Non-BRCA HRR Mutations

• Patients with other HRR gene alterations (excluding BRCA1/2) also saw an OS improvement but with less statistical certainty.
• Median OS was 42.4 months with talazoparib + enzalutamide versus 32.6 months in the placebo group.

Clinical Implications

These findings establish talazoparib plus enzalutamide as a standard-of-care option for HRR-deficient mCRPC, particularly in BRCA1/2-mutated cases, where survival benefits are most substantial. The improvement seen in non-BRCA HRR-deficient patients suggests a broader potential role for PARP inhibition.

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