According to updated results from the phase 3 TALAPRO-2 trial, first-line talazoparib plus enzalutamide significantly improved survival for patients with metastatic castration-resistant prostate cancer (mCRPC) unselected for HRR gene alterations. 

These results were presented by Neeraj Agarwal, MD, Huntsman Cancer Institute, Salt Lake City, Utah, at the 2025 ASCO Genitourinary Cancers Symposium in San Francisco, California.

This study enrolled 805 patients with asymptomatic or mildly symptomatic mCRPC receiving androgen deprivation therapy who had not undergone prior lines of life-prolonging therapy. Patients were randomized on a 1-to-1 basis to receive 160 mg of enzalutamide plus either 0.5 mg of talazoparib (n = 402) or placebo (n = 403) once daily. Randomization was stratified based on receipt of prior abiraterone or docetaxel and HRR gene alteration status (HRR-deficient, n = 169; HRR–non-deficient or HRR- unknown, n = 636). The primary end point was radiographic progression-free survival (rPFS) by blinded independent central review. Key secondary end points included overall survival (OS) and safety. 

At analysis, median rPFS was 33.1 months in the talazoparib plus enzalutamide arm and 19.5 months in the placebo plus enzalutamide arm (hazard ratio [HR], 0.667; 95% confidence interval [CI] 95%, 0.551 to 0.807; P < .0001). Median OS was 45.8 months and 37 months, respectively (HR, 0.796; 95% CI, 0.661 to 0.958; P = .0155). The most common grade ≥3 treatment-emergent adverse events included anemia (49%) and neutropenia (19%). Treatment-emergent adverse events led to treatment discontinuation in 22% of patients. 

The OS HR was 0.549 (95% CI, 0.364 to 0.826; P = .0035) for patients who were HRR-deficient and 0.878 for patients who were HRR–non-deficient or HRR-unknown (95% CI, 0.713 to 1.080; P = .218). Among patients with circulating tumor DNA and tumor tissue results available, the OS HR was 0.749 (95% CI, 0.582 to 0.963; P = .024) for patients without BRCA1/2 alterations (n = 439) and 0.782 (95% CI, 0.582 to 1.050; P = .101) for patients without HRR alterations (n = 314). 

As Dr Agarwal et al concluded, talazoparib plus enzalutamide “demonstrated a statistically significant and clinically meaningful improvement in OS vs standard-of-care [enzalutamide] as [first-line] treatment in [patients] with mCRPC unselected for HRR gene alterations.” 

Source: 

Agarwal N, Azad A, Carles J, et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. Presented at the 2025 ASCO Genitourinary Cancers Symposium. San Francisco, California. February 13-15, 2025. Abstract LBA18