# TALAPRO-2

Source: https://onco.cc/trials/talapro-2/  
OnCo record `talapro-2` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The PARP-plus-hormone combination that eventually showed an overall survival benefit, in 2024-25.

## Summary

TALAPRO-2, trial NCT03395197 sponsored by Pfizer and reported in 2023, is the PARP inhibitor plus hormone therapy combination that eventually showed an overall survival benefit, reported between 2024 and 2025. It randomised 805 unselected men with first-line metastatic castration-resistant prostate cancer to enzalutamide with talazoparib or placebo, met its primary radiographic progression-free survival endpoint with a larger effect in the homologous recombination repair-mutant cohort, and at the final analysis showed improved survival in both populations, though the 2023 FDA approval was limited to HRR-mutant disease. OnCo links it to BRCA1 and BRCA2 and PARP as targets, to talazoparib and enzalutamide. As the only such combination with a significant all-comer survival benefit, whether that finding widens the label is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Registry id: NCT03395197
- Phase: 3
- Setting: First-line mCRPC: enzalutamide + talazoparib vs enzalutamide + placebo (all-comers and HRR-mutant cohorts)
- Sponsor: Pfizer
- Enrolled: 805
- Result: rPFS HR 0.63 (ITT); OS HR 0.80 (ITT), 0.62 (HRR-mutant).
- Outcomes: Radiographic progression-free survival, all comers: Talazoparib + enzalutamide vs Placebo + enzalutamide 21.9 months, HR 0.63; Overall survival, all comers (final): Talazoparib + enzalutamide 45.8 months vs Placebo + enzalutamide 37 months, HR 0.8
- Replication: Consistent with PROpel and MAGNITUDE; the only PARP + ARPI combination with a significant all-comer OS benefit.

## Notes

- In England NICE TA1130 recommends talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer only when chemotherapy is not clinically indicated and abiraterone with prednisolone is either not tolerated or precluded by a clinical condition, and only with the companies' commercial arrangements. Treatment started before publication is not affected. Funding must be available in England within 90 days of publication.

## Sources

- ClinicalTrials.gov NCT03395197: https://clinicaltrials.gov/study/NCT03395197
- NICE TA1130: talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer: https://www.nice.org.uk/guidance/ta1130

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Talazoparib](https://onco.cc/drugs/talazoparib/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- terms: [Prostate cancer drugs in England: what NICE recommends, and what it refuses](https://onco.cc/terms/prostate-uk-drug-approvals/), [Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters](https://onco.cc/terms/prostate-hrr-eligibility/)
- trials: [MAGNITUDE](https://onco.cc/trials/magnitude/), [PROpel](https://onco.cc/trials/propel/), [TRITON3](https://onco.cc/trials/triton3/)
- people: [Neeraj Agarwal](https://onco.cc/people/neeraj-agarwal/)
- key papers: [Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial](https://onco.cc/key-papers/paper-talapro-2-lancet-2023/), [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](https://onco.cc/key-papers/paper-talapro-2-lancet-2025-update/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)

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