TALAPRO-3 showed rPFS benefit in mCSPC
By Agata Buczak
Talazoparib plus enzalutamide significantly improved radiographic progression-free survival (rPFS) compared with placebo plus enzalutamide in patients with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations.
Results come from the phase 3 TALAPRO-3 trial presented at the American Society of Clinical Oncology (ASCO) 2026 Annual Meeting. Presenting the results, Neeraj Agarwal (University of Utah, Salt Lake City, UT, USA) reported that, at data cutoff, the talazoparib combination did not reach median rPFS, compared with 45.8 months with placebo plus enzalutamide (hazard ratio [HR] 0.481).
TALAPRO-3 evaluates the combination earlier in the disease course in men with HRR-altered mCSPC, building on findings from TALAPRO-2, which showed improved rPFS and overall survival (OS) with talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer, with the greatest benefit observed in the HRR-deficient cohort.
Subgroup analyses showed rPFS benefit in both molecular subgroups. In the breast cancer gene (BRCA)-mutated subgroup, the HR for rPFS was 0.368, while in the non–BRCA-mutated subgroup it was 0.567. Interim OS analysis favored talazoparib plus enzalutamide, but statistical significance had not been reached at the time of reporting; there were 74 deaths in the talazoparib arm and 91 in the placebo arm.
The trial randomized 599 patients 1:1 to talazoparib 0.5 mg (0.35 mg in moderate renal impairment) or placebo, both given with enzalutamide 160 mg once daily. Eligible patients had HRR-altered mCSPC and were receiving androgen-deprivation therapy with no prior chemotherapy for metastatic disease.
The most common adverse events included anemia, fatigue, and hematologic toxicities such as neutropenia. Events were generally manageable with dose modifications, although 18.7% of patients discontinued talazoparib due to treatment-emergent adverse events.
The investigators concluded that talazoparib plus enzalutamide led to a statistically significant and clinically meaningful improvement in rPFS, with a trend toward improved OS, in patients with HRR-deficient mCSPC.
Longer-term follow-up, including OS analyses, will further clarify the clinical impact of this combination in HRR-altered mCSPC.
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