# TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer

Source: https://onco.cc/key-papers/paper-fizazi-triton3-rucaparib-nejm-2023/  
OnCo record `paper-fizazi-triton3-rucaparib-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The randomised confirmation that a PARP inhibitor beats the alternatives in men with a BRCA fault, nearly doubling the time before the cancer grew on scans. In men with an ATM fault instead, it did nothing.

## Summary

Karim Fizazi and the TRITON3 investigators randomised 405 men with metastatic castration-resistant prostate cancer and a BRCA1, BRCA2 or ATM alteration, after progression on a second-generation androgen receptor pathway inhibitor, in a 2 to 1 ratio to rucaparib or a physician's choice control of docetaxel, abiraterone or enzalutamide.

The trial answers two questions. In the BRCA subgroup, imaging-based progression-free survival was 11.2 against 6.4 months, hazard ratio 0.50. In the exploratory ATM subgroup it was 8.1 against 6.8 months with a hazard ratio of 0.95, which is to say no effect. The lesson is that homologous recombination repair is not one biomarker: grouping ATM with BRCA in a single test result and treating on it will produce treatment that does not work. The screening figure is also worth noting: 4,855 men were prescreened or screened to randomise 405.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Also known as: TRITON3; Fizazi 2023 rucaparib randomised
- Tags: prostate-evidence
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/nejmoa2214676
- Authors: Fizazi K, Piulats JM, Reaume MN, et al.
- Findings: Of 4,855 men who underwent prescreening or screening, 270 were assigned to rucaparib and 135 to a control medication; 201 and 101 respectively had a BRCA alteration.; At 62 months, imaging-based progression-free survival in the BRCA subgroup was 11.2 months with rucaparib against 6.4 months with control (hazard ratio 0.50; 95 percent confidence interval 0.36 to 0.69).; In the intention-to-treat population it was 10.2 against 6.4 months (hazard ratio 0.61; 0.47 to 0.80; P less than 0.001 for both comparisons).; In the exploratory ATM subgroup, imaging-based progression-free survival was 8.1 months with rucaparib against 6.8 months with control (hazard ratio 0.95; 0.59 to 1.52).; The most frequent adverse events with rucaparib were fatigue and nausea.
- What it means: The randomised proof for PARP inhibition in BRCA-altered prostate cancer, and the clearest evidence that the homologous recombination repair gene list should not be used as a single yes-or-no test. ATM-altered disease needs a different answer, and does not yet have one.
- Caveats: The primary endpoint is imaging-based progression-free survival, not overall survival; the control arm allowed another androgen receptor pathway inhibitor, which is a weak comparator after progression on one.; 4,855 men screened for 405 randomised shows how much testing capacity a biomarker-selected trial in this disease consumes.; The ATM result is exploratory and the subgroup is small, but it points the same way as every other dataset in the field.

## Sources

- N Engl J Med 2023: https://doi.org/10.1056/nejmoa2214676
- PubMed: https://pubmed.ncbi.nlm.nih.gov/36795891/
- ClinicalTrials.gov NCT02975934: https://clinicaltrials.gov/study/NCT02975934

## Connected records

- key papers: [Inherited DNA-repair gene mutations in men with metastatic prostate cancer](https://onco.cc/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/), [PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations](https://onco.cc/key-papers/paper-profound-nejm-2020/), [Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours](https://onco.cc/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/), [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/), [TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration](https://onco.cc/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/)
- roadmaps: [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/)
- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [ATM](https://onco.cc/targets/atm/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- drugs: [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Rucaparib](https://onco.cc/drugs/rucaparib/)
- companies: [Clovis Oncology](https://onco.cc/companies/clovis-oncology/)
- terms: [Genome-wide loss of heterozygosity (gLOH)](https://onco.cc/terms/genome-wide-loss-of-heterozygosity/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Radiographic progression-free survival (rPFS)](https://onco.cc/terms/radiographic-progression-free-survival/), [Synthetic lethality](https://onco.cc/terms/synthetic-lethality/)
- people: [Karim Fizazi](https://onco.cc/people/karim-fizazi/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- ideas: [Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later](https://onco.cc/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/)

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