TALAPRO-2
Talazoparib plus enzalutamide versus placebo plus enzalutamide as first-line therapy for metastatic castration-resistant prostate cancer
Phase 3NCT03395197
- Population
- First-line metastatic castration-resistant prostate cancer without previous life-prolonging systemic therapy for castration-resistant disease: a cohort unselected for HRR gene alterations and an HRR-deficient cohort
- Design
- Randomised (1:1), double-blind, placebo-controlled phase 3 trial of talazoparib 0.5 mg or placebo plus enzalutamide 160 mg once daily (enzalutamide open-label) as first-line therapy in asymptomatic or mildly symptomatic mCRPC with ongoing androgen deprivation. The genetically unselected cohort enrolled 805 patients (402 and 403); a separate HRR-deficient cohort randomised 399 patients (200 and 199). The primary endpoint was radiographic progression-free survival by blinded independent central review; overall survival was an alpha-protected key secondary endpoint.
- Primary endpoint
- rPFS
- Arms
- Talazoparib plus enzalutamide (experimental): Talazoparib 0.5 mg plus enzalutamide 160 mg, orally once daily
- Placebo plus enzalutamide (control): Placebo plus enzalutamide 160 mg, orally once daily
- People
- Agarwal N
rPFSHR 0.63 (95% CI 0.51–0.78)OSHR 0.80 (95% CI 0.66–0.96)Δ median OS+8.8 monthsOSHR 0.88 (95% CI 0.71–1.08)rPFSHR 0.67 (95% CI 0.55–0.81)Δ median rPFS+13.6 months
Show the numbers
| Endpoint | Analysis | Talazoparib plus enzalutamide | Placebo plus enzalutamide | Effect |
|---|---|---|---|---|
| rPFSITT, genetically unselected cohortRadiographic progression-free survival by blinded independent central review | primaryAgarwal 2023 | — | median 21.9 months (16.6–25.1) | HR 0.63 (95% CI 0.51–0.78)P<0.0001Median rPFS for talazoparib plus enzalutamide was not reached (95% CI 27.5 months to not reached). Median follow-up for rPFS was 24.9 months (talazoparib) and 24.6 months (placebo). |
| OSITT, genetically unselected cohort | finalmedian follow-up 52.5 monthsAgarwal 2025 | median 45.8 months (39.4–50.8) | median 37 months (34.1–40.4) | HR 0.80 (95% CI 0.66–0.96)P=0.016Final prespecified overall survival analysis; the alpha threshold at the final analysis was 0.022 (two-sided). |
| OSHRR-non-deficient or unknown patients in the unselected cohort (n=636) | finalAgarwal 2025 | — | — | HR 0.88 (95% CI 0.71–1.08)P=0.22Subgroup analysis; the interval includes 1. |
| rPFSITT, genetically unselected cohortRadiographic progression-free survival by blinded independent central review | long term-updateAgarwal 2025 | median 33.1 months | median 19.5 months | HR 0.67 (95% CI 0.55–0.81)P<0.0001Updated descriptive analysis. |
| OSHRR-deficient cohort (n=399) | finalmedian follow-up 44.2 monthsFizazi 2025 | median 45.1 months | median 31.1 months (27.3–35.4) | HR 0.62 (95% CI 0.48–0.81)P=0.0005Final prespecified overall survival analysis; two-sided p of 0.024 or less was required for significance. The 95% CI for the talazoparib median is 35.4 to not reached. |
| OSBRCA1/2 alterations within the HRR-deficient cohort (n=155) | finalFizazi 2025 | 53% at 4 y | median 28.5 months; 23% at 4 y | HR 0.50 (95% CI 0.32–0.78)P=0.0017Median overall survival not reached for talazoparib plus enzalutamide; 4-year overall survival 53% vs 23%. Subgroup analysis. |
| rPFSHRR-deficient cohort (n=399)Radiographic progression-free survival by blinded independent central review | long term-updateFizazi 2025 | median 30.7 months | median 12.3 months | HR 0.47 (95% CI 0.36–0.61)P<0.0001Updated descriptive analysis. |
| Endpoint | Analysis | Talazoparib plus enzalutamide | Placebo plus enzalutamide | Effect |
|---|---|---|---|---|
| rPFSITT, genetically unselected cohortRadiographic progression-free survival by blinded independent central review | primaryAgarwal 2023 | — | median 21.9 months (16.6–25.1) | HR 0.63 (95% CI 0.51–0.78)P<0.0001Median rPFS for talazoparib plus enzalutamide was not reached (95% CI 27.5 months to not reached). Median follow-up for rPFS was 24.9 months (talazoparib) and 24.6 months (placebo). |
| OSITT, genetically unselected cohort | finalmedian follow-up 52.5 monthsAgarwal 2025 | median 45.8 months (39.4–50.8) | median 37 months (34.1–40.4) | HR 0.80 (95% CI 0.66–0.96)P=0.016Final prespecified overall survival analysis; the alpha threshold at the final analysis was 0.022 (two-sided). |
| OSHRR-non-deficient or unknown patients in the unselected cohort (n=636) | finalAgarwal 2025 | — | — | HR 0.88 (95% CI 0.71–1.08)P=0.22Subgroup analysis; the interval includes 1. |
| rPFSITT, genetically unselected cohortRadiographic progression-free survival by blinded independent central review | long term-updateAgarwal 2025 | median 33.1 months | median 19.5 months | HR 0.67 (95% CI 0.55–0.81)P<0.0001Updated descriptive analysis. |
| OSHRR-deficient cohort (n=399) | finalmedian follow-up 44.2 monthsFizazi 2025 | median 45.1 months | median 31.1 months (27.3–35.4) | HR 0.62 (95% CI 0.48–0.81)P=0.0005Final prespecified overall survival analysis; two-sided p of 0.024 or less was required for significance. The 95% CI for the talazoparib median is 35.4 to not reached. |
| OSBRCA1/2 alterations within the HRR-deficient cohort (n=155) | finalFizazi 2025 | 53% at 4 y | median 28.5 months; 23% at 4 y | HR 0.50 (95% CI 0.32–0.78)P=0.0017Median overall survival not reached for talazoparib plus enzalutamide; 4-year overall survival 53% vs 23%. Subgroup analysis. |
| rPFSHRR-deficient cohort (n=399)Radiographic progression-free survival by blinded independent central review | long term-updateFizazi 2025 | median 30.7 months | median 12.3 months | HR 0.47 (95% CI 0.36–0.61)P<0.0001Updated descriptive analysis. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| rPFS | 0.63 | 0.51–0.78 |
| OS | 0.8 | 0.66–0.96 |
| OS | 0.88 | 0.71–1.08 |
| rPFS | 0.67 | 0.55–0.81 |
| OS | 0.62 | 0.48–0.81 |
| OS | 0.5 | 0.32–0.78 |
| rPFS | 0.47 | 0.36–0.61 |
- Placebo plus enzalutamide (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Placebo plus enzalutamide |
|---|---|
| 0 | 100.0% |
| 14 | 64.2% |
| 27 | 42.5% |
| 41 | 27.3% |
| 55 | 17.5% |
- Talazoparib plus enzalutamide (experimental)
- Placebo plus enzalutamide (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Talazoparib plus enzalutamide | Placebo plus enzalutamide |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 29 | 64.5% | 58.1% |
| 57 | 42.2% | 34.4% |
| 86 | 27.2% | 20.0% |
| 115 | 17.5% | 11.6% |
Appears in
Sources
Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023;402(10398):291-303.
Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Szczylik C, 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):447-460.
Fizazi K, Azad AA, Matsubara N, Carles J, Fay AP, De Giorgi U, et al. Talazoparib plus enzalutamide in men with HRR-deficient metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial. Lancet. 2025;406(10502):461-474.