According to results from the phase 3 TALAPRO-2 trial, the addition of talazoparib to enzalutamide improved the overall survival (OS) among patients with homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting, compared with enzalutamide alone.

These results were first presented by Karim Fizazi, MD, Gustave-Roussy Institute, Paris, France, at the 2025 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California.

This trial enrolled 399 patients with HRR-deficient mCRPC who had ongoing androgen deprivation therapy and had not had prior life-prolonging therapy for CRPC. Patients were randomized on a 1-to-1 basis to receive 160 mg enzalutamide with either 0.5 mg talazoparib (n = 200) or placebo (n = 199) daily. Randomization was stratified by prior abiraterone/docetaxel treatment for castration-sensitive prostate cancer. As previously reported, the trial met its primary end point of radiographic progression-free survival (rPFS) by blinded independent central review. This analysis reports the secondary end point of OS.

The median follow-up duration was 44.2 months in the talazoparib arm and 44.4 months in the placebo arm. The OS hazard ratio [HR] was 0.622 (2-sided P = .0005) for the talazoparib arm vs the placebo arm. The median OS was 45.1 months vs 31.1 months, respectively. In exploratory analysis, the OS favored talazoparib plus enzalutamide vs placebo plus enzalutamide for patients both with and without BRCA1/2 alterations (with BRCA1/2 alterations, n = 155; HR = .497, P = .0017; without BRCA1/2 alterations, n = 244; HR = 0.727, P = .0665). The median rPFS was 30.7 months in the talazoparib arm vs 12.3 months in the placebo arm. The safety profile was consistent with primary results.

Dr Fizazi and coauthors concluded that talazoparib plus enzalutamide “demonstrated a statistically significant and clinically meaningful improvement in OS” compared to enzalutamide alone, and that these data establish talazoparib plus enzalutamide “as a standard of care for [first-line] treatment in [patients] with HRR-deficient mCRPC).

Source:

Fizazi K, Azad A, Matsubara N, et al. Final overall survival (OS) with talazoparib (TALA) + enzolutamide (ENZA) as first-line (1L) treatment in patients (pts) with homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. Presented at the 2025 ASCO Genitourinary Cancers Symposium. February 13-15, 2025; San Francisco, CA. Abstract LBA141.