# TRITON3

Source: https://onco.cc/trials/triton3/  
OnCo record `triton3` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A PARP inhibitor works for men whose prostate cancer carries a BRCA fault, and does not work for men whose fault is in ATM. Which gene is broken decides whether the drug helps.

## Summary

TRITON3 is the cleanest demonstration in prostate cancer that homologous recombination repair is not one thing. Of 4,855 men prescreened or screened, 405 were randomised 2:1 to rucaparib 600 mg twice daily (270) or physician's choice of docetaxel or a second androgen receptor pathway inhibitor (135). Of these, 201 and 101 had a BRCA alteration.

At 62 months, imaging-based progression-free survival was significantly longer with rucaparib in the BRCA subgroup, median 11.2 against 6.4 months, hazard ratio 0.50 (95 percent confidence interval 0.36 to 0.69), and in the intention-to-treat population, 10.2 against 6.4 months, hazard ratio 0.61 (0.47 to 0.80), p<0.001 for both.

In the exploratory ATM subgroup, median imaging-based progression-free survival was 8.1 months with rucaparib and 6.8 months with control, hazard ratio 0.95 (0.59 to 1.52). That is no effect. ATM is routinely counted as a homologous recombination repair gene on panel reports, and TRITON3 is the evidence that counting it that way over-promises.

The most frequent adverse events with rucaparib were fatigue and nausea. The screening ratio, 4,855 to 405, is worth quoting to any man being offered genomic testing: the eligible genotype is uncommon, and a negative result is the usual result.

## Fields

- Kind: Trial
- Status: mixed
- Last checked: 2026-09-25
- Also known as: TRITON3; rucaparib in BRCA or ATM altered mCRPC
- Registry id: NCT02975934
- Phase: 3
- Setting: Metastatic castration-resistant prostate cancer with a BRCA1, BRCA2 or ATM alteration and progression after a second-generation androgen receptor pathway inhibitor: rucaparib 600 mg twice daily against physician's choice of docetaxel or a second androgen receptor pathway inhibitor, randomised 2:1, with imaging-based progression-free survival by independent review as the primary outcome
- Sponsor: Clovis Oncology
- Enrolled: 405
- Result: Median imaging-based progression-free survival 11.2 against 6.4 months in the BRCA subgroup (hazard ratio 0.50, 95 percent confidence interval 0.36 to 0.69) and 10.2 against 6.4 months overall (0.61, 0.47 to 0.80); no effect in the ATM subgroup (0.95, 0.59 to 1.52).
- Outcomes: Imaging-based progression-free survival, BRCA subgroup (median): Rucaparib 600 mg twice daily 11.2 months vs Physician's choice 6.4 months, HR 0.5; Imaging-based progression-free survival, intention to treat (median): Rucaparib 600 mg twice daily 10.2 months vs Physician's choice 6.4 months, HR 0.61; Imaging-based progression-free survival, ATM subgroup (median): Rucaparib 600 mg twice daily 8.1 months vs Physician's choice 6.8 months, HR 0.95
- Replication: PROfound found the same gene-dependence, with a larger effect in BRCA1, BRCA2 and ATM combined than in the wider homologous recombination repair panel; PROpel, MAGNITUDE and TALAPRO-2 tested PARP inhibitors with an androgen receptor pathway inhibitor in the first line.

## Sources

- ClinicalTrials.gov NCT02975934: https://clinicaltrials.gov/study/NCT02975934
- 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

## 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: [Rucaparib](https://onco.cc/drugs/rucaparib/)
- companies: [Clovis Oncology](https://onco.cc/companies/clovis-oncology/)
- terms: [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [What follows what in castration-resistant prostate cancer](https://onco.cc/terms/prostate-crpc-sequencing/), [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/), [PROfound](https://onco.cc/trials/profound/), [PROpel](https://onco.cc/trials/propel/), [TALAPRO-2](https://onco.cc/trials/talapro-2/)

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