TRITON3
Rucaparib versus physician's choice of therapy in metastatic castration-resistant prostate cancer with homologous recombination gene deficiency
Phase 3N = 405NCT02975934
- Population
- Metastatic castration-resistant prostate cancer with a BRCA1, BRCA2 or ATM alteration and progression after a second-generation androgen-receptor pathway inhibitor; 270 randomised to rucaparib and 135 to control (BRCA alteration: 201 and 101)
- Design
- Randomised (2:1) phase 3 trial of oral rucaparib 600 mg twice daily versus a physician's-choice control (docetaxel or a second-generation androgen-receptor pathway inhibitor: abiraterone acetate or enzalutamide) in men with a BRCA1, BRCA2 or ATM alteration whose disease progressed after a second-generation ARPI. The primary outcome was imaging-based progression-free survival by independent review.
- Primary endpoint
- rPFS
- Arms
- Rucaparib (experimental, n = 270): Rucaparib 600 mg orally twice daily
- Physician's choice (control, n = 135): Docetaxel or a second-generation ARPI (abiraterone acetate or enzalutamide)
- People
- Fizazi K
rPFSHR 0.50 (95% CI 0.36–0.69)Δ median rPFS+4.8 monthsrPFSHR 0.61 (95% CI 0.47–0.80)Δ median rPFS+3.8 monthsrPFSHR 0.95 (95% CI 0.59–1.52)Δ median rPFS+1.3 months
Show the numbers
| Endpoint | Analysis | Rucaparib | Physician's choice | Effect |
|---|---|---|---|---|
| rPFSBRCA subgroup (201 rucaparib, 101 control)Imaging-based progression-free survival by independent review | primaryFizazi 2023 | median 11.2 months | median 6.4 months | HR 0.50 (95% CI 0.36–0.69)P<0.001The abstract gives P<0.001 for both the BRCA-subgroup and the intention-to-treat comparisons. |
| rPFSImaging-based progression-free survival by independent review | primaryFizazi 2023 | median 10.2 months | median 6.4 months | HR 0.61 (95% CI 0.47–0.80)P<0.001Intention-to-treat population: 270 rucaparib, 135 control. |
| rPFSATM subgroupImaging-based progression-free survival by independent review | exploratoryFizazi 2023 | median 8.1 months | median 6.8 months | HR 0.95 (95% CI 0.59–1.52)Exploratory analysis; the interval includes 1. |
| OSBRCA subgroup (302 patients; 162 deaths, data maturity 54%) | interimFizazi 2023 | median 24.3 months (19.9–25.7) | median 20.8 months (16.3–23.1) | HR 0.81 (95% CI 0.58–1.12)P=0.21Interim overall survival analysis conducted with the imaging-based PFS analysis; log-rank P=0.21. In the intention-to-treat population 240 of 405 patients had died (data maturity 59%). Not in the PubMed abstract. |
| OSBRCA-mutated subgroup (302 patients; analysis cutoff not stated in the FDA notice) | long term-updateSource 2025 | median 23.2 months (19.1–25.2) | median 21.2 months (18.0–23.1) | HR 0.91 (95% CI 0.68–1.20)Read from the FDA notice of 17 December 2025 (basis recorded as label; the field has no value for an FDA web notice). Not the paper's interim analysis (see os-brca-interim: 24.3 vs 20.8 months, HR 0.81); the notice does not state its cutoff or maturity, and the label 'long-term-update' is chosen because its medians differ from the interim analysis. The notice describes the difference as not significant; in the exploratory ATM subgroup it gives an OS hazard ratio of 1.21 (95% CI 0.77 to 1.90). |
| Endpoint | Analysis | Rucaparib | Physician's choice | Effect |
|---|---|---|---|---|
| rPFSBRCA subgroup (201 rucaparib, 101 control)Imaging-based progression-free survival by independent review | primaryFizazi 2023 | median 11.2 months | median 6.4 months | HR 0.50 (95% CI 0.36–0.69)P<0.001The abstract gives P<0.001 for both the BRCA-subgroup and the intention-to-treat comparisons. |
| rPFSImaging-based progression-free survival by independent review | primaryFizazi 2023 | median 10.2 months | median 6.4 months | HR 0.61 (95% CI 0.47–0.80)P<0.001Intention-to-treat population: 270 rucaparib, 135 control. |
| rPFSATM subgroupImaging-based progression-free survival by independent review | exploratoryFizazi 2023 | median 8.1 months | median 6.8 months | HR 0.95 (95% CI 0.59–1.52)Exploratory analysis; the interval includes 1. |
| OSBRCA subgroup (302 patients; 162 deaths, data maturity 54%) | interimFizazi 2023 | median 24.3 months (19.9–25.7) | median 20.8 months (16.3–23.1) | HR 0.81 (95% CI 0.58–1.12)P=0.21Interim overall survival analysis conducted with the imaging-based PFS analysis; log-rank P=0.21. In the intention-to-treat population 240 of 405 patients had died (data maturity 59%). Not in the PubMed abstract. |
| OSBRCA-mutated subgroup (302 patients; analysis cutoff not stated in the FDA notice) | long term-updateSource 2025 | median 23.2 months (19.1–25.2) | median 21.2 months (18.0–23.1) | HR 0.91 (95% CI 0.68–1.20)Read from the FDA notice of 17 December 2025 (basis recorded as label; the field has no value for an FDA web notice). Not the paper's interim analysis (see os-brca-interim: 24.3 vs 20.8 months, HR 0.81); the notice does not state its cutoff or maturity, and the label 'long-term-update' is chosen because its medians differ from the interim analysis. The notice describes the difference as not significant; in the exploratory ATM subgroup it gives an OS hazard ratio of 1.21 (95% CI 0.77 to 1.90). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| rPFS | 0.5 | 0.36–0.69 |
| rPFS | 0.61 | 0.47–0.8 |
| rPFS | 0.95 | 0.59–1.52 |
| OS | 0.81 | 0.58–1.12 |
| OS | 0.91 | 0.68–1.2 |
- Rucaparib (experimental)
- Physician's choice (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Rucaparib | Physician's choice |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 64.8% | 46.9% |
| 14 | 42.0% | 22.0% |
| 21 | 27.3% | 10.3% |
| 28 | 17.7% | 4.8% |
- Rucaparib (experimental)
- Physician's choice (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Rucaparib | Physician's choice |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 66.5% | 52.2% |
| 13 | 41.3% | 24.5% |
| 19 | 27.5% | 12.8% |
| 26 | 17.1% | 6.0% |
Appears in
Sources
Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, et al. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023;388(8):719-732.
FDA. FDA grants regular approval to rucaparib for metastatic castration-resistant prostate cancer. Notice, 17 December 2025.