TALAPRO-3 data show talazoparib plus enzalutamide delayed progression in HRR-deficient metastatic castration-sensitive prostate cancer.
TALAPRO-3 results presented at ASCO showed that adding talazoparib to enzalutamide significantly improved radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer harboring homologous recombination repair gene alterations.
The Phase 3, double-blind trial randomized 599 patients to receive talazoparib plus enzalutamide or placebo plus enzalutamide. Patients were stratified by de novo versus relapsed disease, high-volume versus low-volume disease, and BRCA versus non-BRCA mutational status. Eligible patients had an ECOG performance status of 0 or 1, ongoing androgen deprivation therapy (ADT), and confirmed HRR gene alterations through tumor tissue and/or circulating tumor DNA testing.
Strongest Signal Seen in BRCA-Mutated Disease
At a median follow-up of 37.6 months in the talazoparib plus enzalutamide group and 37.7 months in the placebo plus enzalutamide group, the combination significantly improved investigator-assessed radiographic progression-free survival. Median rPFS was not reached with talazoparib plus enzalutamide compared with 45.8 months with placebo plus enzalutamide.
The treatment effect translated to a hazard ratio of 0.481, with a 95% CI of 0.357–0.647 and a 2-sided P value of <0.0001. Benefit was observed across mutational subgroups, with a more pronounced rPFS effect in patients with BRCA-mutated disease. In this subgroup, the hazard ratio was 0.368, compared with 0.567 in the non-BRCA-mutated subgroup.
Overall Survival Trend Favors Combination
Interim overall survival data favored talazoparib plus enzalutamide, although statistical significance has not yet been reached. There were 74 deaths in the talazoparib plus enzalutamide group and 91 deaths in the placebo plus enzalutamide group, corresponding to a hazard ratio of 0.767.
The safety profile was generally manageable and consistent with the known profiles of both agents. The most common all-grade treatment-emergent adverse events with talazoparib plus enzalutamide were anemia, fatigue, decreased neutrophil count, neutropenia, asthenia, and decreased white blood cell count. No new safety signals were identified. Treatment-emergent adverse events were generally managed with dose modifications, although 18.7% of patients discontinued talazoparib because of adverse events.
Together, the TALAPRO-3 findings support talazoparib plus enzalutamide as a clinically meaningful strategy for patients with HRR-deficient metastatic castration-sensitive prostate cancer, while longer follow-up will clarify the overall survival impact.
Reference
Agarwal N 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. ASCO Annual Meeting, May 29-June 2, 2026.
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