MAGNITUDE
Niraparib with abiraterone acetate and prednisone versus placebo with abiraterone acetate and prednisone in metastatic castration-resistant prostate cancer
Phase 3NCT03748641
- Population
- Treatment-naive metastatic castration-resistant prostate cancer, with and without HRR gene alterations
- Design
- Randomised (1:1), double-blind phase 3 study of niraparib plus abiraterone acetate and prednisone (niraparib + AAP) versus placebo + AAP, in patients with (HRR+, n=423) or without (HRR-, n=247) homologous recombination repair gene alterations determined prospectively by tissue or plasma assays. The primary endpoint, radiographic progression-free survival by central review, was tested first in the BRCA1/2 subgroup and then in the full HRR+ cohort. A futility analysis was prespecified in the HRR- cohort.
- Primary endpoint
- rPFS
- Arms
- Niraparib plus AAP (experimental, n = 212): Niraparib plus abiraterone acetate and prednisone
- Placebo plus AAP (control, n = 211): Placebo plus abiraterone acetate and prednisone
- People
- Chi KN
rPFSHR 0.53 (95% CI 0.36–0.79)Δ median rPFS+5.7 monthsrPFSHR 0.73 (95% CI 0.56–0.96)Δ median rPFS+2.8 monthsOSHR 0.931 (95% CI 0.720–1.203)OSHR 0.788 (95% CI 0.554–1.120)
Show the numbers
| Endpoint | Analysis | Niraparib plus AAP | Placebo plus AAP | Effect |
|---|---|---|---|---|
| rPFSBRCA1/2 subgroup of the HRR+ cohortRadiographic progression-free survival by central review | primaryChi 2023 | median 16.6 months | median 10.9 months | HR 0.53 (95% CI 0.36–0.79)P=0.001 |
| rPFSHRR+ cohort (n=423)Radiographic progression-free survival by central review | primaryChi 2023 | median 16.5 months | median 13.7 months | HR 0.73 (95% CI 0.56–0.96)P=0.022 |
| OSHRR+ cohort (niraparib + AAP n=212, placebo + AAP n=211) | finalmedian follow-up 37.3 monthsChi 2025 | — | — | HR 0.931 (95% CI 0.720–1.203)P=0.585Prespecified, event-driven final analysis of secondary efficacy endpoints; the abstract reports no difference in overall survival. A prespecified multivariate analysis adjusted for baseline prognostic factors gave a hazard ratio of 0.785 (95% CI 0.606 to 1.016; nominal p=0.066). |
| OSBRCA1/2 subgroup of the HRR+ cohort | finalmedian follow-up 37.3 monthsChi 2025 | — | — | HR 0.788 (95% CI 0.554–1.120)P=0.183 (nominal)Nominal p-value as published. The adjusted multivariate hazard ratio in the BRCA1/2 subgroup was 0.663 (95% CI 0.464 to 0.947; nominal p=0.024). |
| Endpoint | Analysis | Niraparib plus AAP | Placebo plus AAP | Effect |
|---|---|---|---|---|
| rPFSBRCA1/2 subgroup of the HRR+ cohortRadiographic progression-free survival by central review | primaryChi 2023 | median 16.6 months | median 10.9 months | HR 0.53 (95% CI 0.36–0.79)P=0.001 |
| rPFSHRR+ cohort (n=423)Radiographic progression-free survival by central review | primaryChi 2023 | median 16.5 months | median 13.7 months | HR 0.73 (95% CI 0.56–0.96)P=0.022 |
| OSHRR+ cohort (niraparib + AAP n=212, placebo + AAP n=211) | finalmedian follow-up 37.3 monthsChi 2025 | — | — | HR 0.931 (95% CI 0.720–1.203)P=0.585Prespecified, event-driven final analysis of secondary efficacy endpoints; the abstract reports no difference in overall survival. A prespecified multivariate analysis adjusted for baseline prognostic factors gave a hazard ratio of 0.785 (95% CI 0.606 to 1.016; nominal p=0.066). |
| OSBRCA1/2 subgroup of the HRR+ cohort | finalmedian follow-up 37.3 monthsChi 2025 | — | — | HR 0.788 (95% CI 0.554–1.120)P=0.183 (nominal)Nominal p-value as published. The adjusted multivariate hazard ratio in the BRCA1/2 subgroup was 0.663 (95% CI 0.464 to 0.947; nominal p=0.024). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| rPFS | 0.53 | 0.36–0.79 |
| rPFS | 0.73 | 0.56–0.96 |
| OS | 0.931 | 0.72–1.203 |
| OS | 0.788 | 0.554–1.12 |
- Niraparib plus AAP (experimental)
- Placebo plus AAP (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Niraparib plus AAP | Placebo plus AAP |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 65.9% | 52.9% |
| 21 | 41.6% | 26.3% |
| 31 | 27.4% | 13.9% |
| 42 | 17.3% | 6.9% |
- Niraparib plus AAP (experimental)
- Placebo plus AAP (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Niraparib plus AAP | Placebo plus AAP |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 65.7% | 60.3% |
| 21 | 41.4% | 34.6% |
| 31 | 27.2% | 20.8% |
| 41 | 17.9% | 12.6% |
Appears in
Sources
Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, et al. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023;41(18):3339-3351.
Chi KN, Castro E, Attard G, Smith MR, Sandhu S, Efstathiou E, et al. Niraparib and Abiraterone Acetate plus Prednisone in Metastatic Castration-resistant Prostate Cancer: Final Overall Survival Analysis for the Phase 3 MAGNITUDE Trial. Eur Urol Oncol. 2025;8(4):986-998.