# Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters

Source: https://onco.cc/terms/prostate-hrr-eligibility/  
OnCo record `prostate-hrr-eligibility` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

PARP inhibitors work in prostate cancer only for men whose tumour carries a fault in a DNA repair gene, and mostly only if that gene is BRCA1 or BRCA2. A fault in ATM, which is often reported on the same panel, does not seem to count.

## Summary

Homologous recombination repair genes are reported together on genomic panels, which encourages the assumption that they behave alike. In prostate cancer they do not, and the trials say so directly.

TRITON3 is the cleanest evidence. It randomised 405 men with a BRCA1, BRCA2 or ATM alteration and progression after a second-generation androgen receptor pathway inhibitor to rucaparib or physician's choice. In the BRCA subgroup, median imaging-based progression-free survival was 11.2 against 6.4 months, hazard ratio 0.50 (95 percent confidence interval 0.36 to 0.69). In the exploratory ATM subgroup it was 8.1 against 6.8 months, hazard ratio 0.95 (0.59 to 1.52): no effect at all. The intention-to-treat figure, 10.2 against 6.4 months, hazard ratio 0.61 (0.47 to 0.80), sits between the two and is diluted by the ATM patients.

The second number worth quoting is the screening ratio. TRITON3 prescreened or screened 4,855 men to randomise 405. A man being offered genomic testing should be told that the usual result is that no eligible alteration is found.

Testing is done on tumour tissue, on circulating tumour DNA, or on blood for germline variants, and all three routes are used because archival prostate biopsy tissue is often too small or too old to yield usable DNA. Germline testing also has implications for a man's relatives, which is a separate conversation and one reason it is offered with genetic counselling.

What this means in England. NICE TA887 recommends olaparib within its marketing authorisation for hormone-relapsed metastatic prostate cancer with BRCA1 or BRCA2 mutations that has progressed after a newer hormonal treatment: the recommendation is explicitly BRCA, not the wider panel. NICE TA951 recommends olaparib with abiraterone and prednisone or prednisolone for untreated hormone-relapsed metastatic prostate cancer in adults who cannot have or do not want chemotherapy, which is an all-comers indication rather than a biomarker-selected one. 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. NICE TA1032, for niraparib with abiraterone acetate and prednisone, is a terminated appraisal: Johnson and Johnson made no evidence submission, so NICE was unable to make any recommendation.

So in England the biomarker-selected route is olaparib after an androgen receptor pathway inhibitor for BRCA-mutated disease, and the combination routes are constrained by what a man cannot otherwise have rather than by what his tumour carries.

## Fields

- Kind: Term
- Status: established
- Last checked: 2026-09-25
- Also known as: HRR eligibility prostate; BRCA testing prostate cancer; PARP inhibitor eligibility prostate

## Sources

- TRITON3 (New England Journal of Medicine 2023): https://doi.org/10.1056/NEJMoa2214676
- NICE TA887: olaparib for previously treated BRCA mutation-positive hormone-relapsed metastatic prostate cancer: https://www.nice.org.uk/guidance/ta887
- NICE TA951: olaparib with abiraterone for untreated hormone-relapsed metastatic prostate cancer: https://www.nice.org.uk/guidance/ta951
- NICE TA1130: talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer: https://www.nice.org.uk/guidance/ta1130
- NICE TA1032: niraparib with abiraterone acetate and prednisone for untreated hormone-relapsed metastatic prostate cancer, terminated appraisal: https://www.nice.org.uk/guidance/terminated/ta1032

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)
- targets: [ATM](https://onco.cc/targets/atm/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/), [Rucaparib](https://onco.cc/drugs/rucaparib/), [Talazoparib](https://onco.cc/drugs/talazoparib/)
- terms: [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/)
- trials: [MAGNITUDE](https://onco.cc/trials/magnitude/), [PROfound](https://onco.cc/trials/profound/), [PROpel](https://onco.cc/trials/propel/), [TALAPRO-2](https://onco.cc/trials/talapro-2/), [TRITON3](https://onco.cc/trials/triton3/)

---
JSON: https://onco.cc/api/v1/entities/prostate-hrr-eligibility.json