Clinical Summary: 

• Design/Population: The phase 3 TALAPRO-3 trial randomized patients with HRR-deficient metastatic castration-sensitive prostate cancer to receive talazoparib plus enzalutamide or placebo plus enzalutamide in combination with ongoing androgen deprivation therapy.
• Key Outcomes: Talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with enzalutamide alone. Benefit was observed in both BRCA-mutated and non-BRCA HRR-altered subgroups.
• Clinical Relevance: These findings support the addition of talazoparib to enzalutamide as a potential new treatment option for patients with HRR-deficient metastatic castration-sensitive prostate cancer. 

Results from the phase 3 TALAPRO-3 trial demonstrated that talazoparib plus enzalutamide significantly improved radiographic progression-free survival (rPFS) compared with enzalutamide alone among patients with HRR-deficient metastatic castration-sensitive prostate cancer.

These results were presented by Neeraj Agarwal, MD, Huntsman Cancer Institute, Salt Lake City, Utah, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this double-blind study, researchers enrolled 599 patients who had no prior docetaxel exposure and had received no more than 3 months of androgen deprivation therapy, with or without an androgen receptor pathway inhibitor. Patients were randomized 1:1 to receive either 0.5 mg of once daily talazoparib (0.35 mg for patients with moderate renal impairment) plus 160 mg of once daily enzalutamide (n = 300) or placebo plus enzalutamide (n = 299), stratified based on disease presentation, disease volume, and BRCA status. Patients were required to continue androgen deprivation therapy. 

The primary end point was investigator-assessed rPFS. Key secondary end points included overall survival (OS) and safety. 

At analysis, median rPFS was not reached in the talazoparib plus enzalutamide arm and 45.8 months in the enzalutamide plus placebo arm (hazard ratio [HR], 0.481; 95% confidence interval [CI], 0.357 to 0.647; P < .0001). The HR for rPFS was 0.368 in BRCA-mutated patients and 0.567 in non-BRCA-mutated patients. With 74 deaths in the talazoparib plus enzalutamide arm and 91 deaths in the enzalutamide plus placebo arm OS did not reach statistical significance. 

No new safety signals were identified. The most frequently reported any-grade treatment-emergent adverse events included anemia (71.2%), fatigue (28.4%), neutrophil count decrease (27.1%), neutropenia (22.1%), asthenia (21.4%), and white blood cell count decrease (21.4%). Treatment-emergent adverse events were manageable with dose modifications, although 18.7% of patients discontinued talazoparib due to treatment-emergent adverse events.

“Treatment with [talazoparib plus enzalutamide] led to a statistically significant and clinically meaningful improvement in the primary end point of rPFS with a trend towards improved OS vs standard-of-care [enzalutamide],” concluded Dr Agarwal. “The safety profile was generally manageable and consistent with those for [talazoparib plus enzalutamide]. ” 

Source: 

Agarwal N, Matsubara N, Azad A, et al. TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA5007.