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PARP inhibitor plus abiraterone helped men with BRCA mutations and did nothing for those without, settling a debate.
MAGNITUDE, trial NCT03748641 sponsored by Janssen and reported in 2022, tested adding the PARP inhibitor niraparib to abiraterone in first-line metastatic castration-resistant prostate cancer in separate cohorts with and without homologous recombination repair alterations, and it settled a debate: the combination helped men with BRCA mutations and did nothing for those without. The HRR-negative cohort was stopped for futility, while the BRCA cohort met its radiographic progression-free survival endpoint and showed a survival benefit at update, and the fixed-dose combination Akeega was approved in 2023 for BRCA-mutant disease. OnCo links it to BRCA1 and BRCA2 as targets, to niraparib and abiraterone acetate. Whether the negative HRR-negative result applies to other PARP inhibitors is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
423 randomised.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Radiographic progression-free survival, BRCA1/2 subgroupprimary | Niraparib + abiraterone | 113 | 16.6 months | 0.53 (0.36 to 0.79) | 0.001 | link |
| Placebo + abiraterone | 112 | 10.9 months |
Shares PROpel, TRITON3, Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters, Prostate cancer drugs in England: what NICE recommends, and what it refuses.
Shares Niraparib, Abiraterone acetate, Johnson & Johnson, PARP inhibitors.
Shares Subgroup analysis (forest plots), Pre-specified vs post-hoc analysis, Futility analysis (stopped for futility), Group sequential design, stopping rules and alpha spending.
Shares Niraparib, Abiraterone acetate, Johnson & Johnson, PARP inhibitors.
Shares Futility analysis (stopped for futility), Data monitoring committee (DSMB, IDMC), Group sequential design, stopping rules and alpha spending.
Shares Futility analysis (stopped for futility), Data monitoring committee (DSMB, IDMC), Group sequential design, stopping rules and alpha spending.
Shares Prostate cancer drugs in England: what NICE recommends, and what it refuses, Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test, Abiraterone acetate, Johnson & Johnson.
Shares Abiraterone acetate, PARP inhibitors, Metastatic castration-resistant prostate cancer, Prostate cancer.