A PHASE 3 trial has demonstrated that combining talazoparib with enzalutamide significantly improves outcomes for men with metastatic castration-resistant prostate cancer (mCRPC). The TALAPRO-2 study enrolled 805 patients from 200 centres across 26 countries, including North America, Europe, Israel, South America, South Africa, and the Asia–Pacific region. Participants were adult men with asymptomatic or mildly symptomatic mCRPC who were receiving ongoing androgen deprivation therapy and had no prior life-prolonging systemic therapy for castration-resistant disease.
Patients were randomly assigned to receive either talazoparib plus enzalutamide or enzalutamide plus placebo, with treatment administered orally once daily. Both patients and investigators were blinded to talazoparib or placebo, while enzalutamide was given openly. The trial’s primary endpoint was radiographic progression-free survival (rPFS), with overall survival (OS) as a key secondary endpoint.
After a median follow-up of 52.5 months, the study found a significant improvement in overall survival with the combination therapy. Median OS was 45.8 months for patients receiving talazoparib plus enzalutamide, compared with 37.0 months for those on enzalutamide plus placebo, representing a hazard ratio of 0.80. Subgroup analysis indicated that patients with homologous recombination repair (HRR) gene alterations derived the greatest benefit, while HRR-non-deficient or unknown patients also showed a favourable trend. Updated rPFS results further supported the combination therapy, with median rPFS of 33.1 months versus 19.5 months for the control group.
Safety outcomes were consistent with the known profile of talazoparib. Grade 3 or higher adverse events were more frequent with the combination, particularly anaemia and neutropenia, but were manageable within clinical practice.
Overall, the TALAPRO-2 findings establish talazoparib combined with enzalutamide as an effective and safe initial treatment option for men with mCRPC. By significantly extending overall survival and delaying disease progression, this combination therapy represents a potential new standard-of-care, offering meaningful clinical benefit for patients regardless of HRR gene alteration status.
Reference
Agarwal N et al. Talazoparib plus enzalutamide in men with metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial. Lancet. 2025;406(10502):447-60.
