SUMMARY

• In MAGNITUDE, the phase 3 study evaluating the efficacy and safety of AKEEGA with prednisone as first-line (L1) therapy in metastatic castration-resistant prostate cancer (mCRPC) for patients with certain homologous recombination repair (HRR) mutations, including BRCA1/2, progression or change in PSA level was not used as a lone indicator for disease progression or treatment discontinuation. For patients who had an increasing PSA in the absence of radiographic or clinical progression, study treatment was continued.^1-3
  • Patients who received abiraterone acetate plus prednisone (AAP) for mCRPC prior to study entry underwent prostate-specific antigen (PSA) testing to document a lack of PSA progression before random assignment.³
  • Patients were prospectively allocated to cohorts based on prescreening for HRR biomarker positive (HRR+) or biomarker negative (HRR-) status and subsequently randomized to receive niraparib or matching placebo in combination with AAP.³
  • Time to PSA progression and PSA response rate were prespecified exploratory endpoints.^4,5 These endpoints were not adjusted for multiple comparisons. Therefore, the P-value is nominal and statistical significance has not been established.
    • At the first interim analysis, after a median follow-up of 16.7 months:³ 
      • HRR+ patients: median time to PSA progression in the niraparib/AAP group was 18.5 months vs 9.3 months in the placebo/AAP group (HR, 0.57; 95% CI, 0.43-0.76; nominal P<0.001).
      • BRCA1/2 subgroup: median time to PSA progression in the niraparib/AAP group was not evaluable (NE) vs 9.2 months in the placebo/AAP group (HR, 0.46; 95% CI, 0.30-0.69; nominal P<0.001).
    • At the second interim analysis, after a median follow-up of 24.8 months, in the BRCA1/2 subgroup:^5,6 
      • Median time to PSA progression in the niraparib/AAP group was 18.4 months vs 9.2 months in the placebo/AAP group (HR, 0.48; 95% CI, 0.33-0.70; nominal P<0.0001).
      • Confirmed PSA response was observed in 89 (78.8%) vs 73 (65.2%) patients in the nira/AAP group vs placebo/AAP group.
    • PSA-related results are provided in Table: PSA Results in the MAGNITUDE Study.
• PSA results have been reported from a post hoc analysis of the MAGNITUDE study that adjusted for imbalances in baseline characteristics using inverse probability of treatment weighting (IPTW) analysis (Table: Unadjusted and Adjusted Time to PSA Progression).^7,8 

CLINICAL DATA

MAGNITUDE Study

Chi et al (2023, 2025)^3,5,9,10 and Efstathiou et al (2023)¹¹ reported the efficacy and safety of AKEEGA with prednisone compared with placebo/AAP in mCRPC for patients with (n=423) and without (n=233) certain HRR mutations, including BRCA1/2 (n=225).

Study Design/Methods

• Phase 3, randomized, double-blind, placebo-controlled, global study
• Patients were randomized 1:1 to receive niraparib 200 mg by mouth (PO) once daily or matching placebo in combination with abiraterone acetate 1000 mg PO once daily plus prednisone 5 mg twice daily. A third, open-label cohort was added to evaluate niraparib 200 mg and abiraterone acetate 1000 mg (dual action tablet formulation) PO once daily with prednisone 5 mg twice daily.

Results

Patient Characteristics

• Baseline characteristics were broadly comparable between treatment arms; however, rates of visceral metastases, bone metastases, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 1 were imbalanced to the disadvantage of the niraparib/AAP group.³
• Baseline PSA levels are shown in Table: Baseline PSA Levels in the MAGNITUDE Study.

Efficacy

• PSA-related results are listed in Table: PSA Results in the MAGNITUDE Study.
• Multivariate analyses (MVA) for rPFS and OS were preplanned. Results for adjusting of baseline variables, including PSA, is summarized in Table; Multivariate Analyses.

Post Hoc Analysis

Roubaud et al (2024)^7,8 reported the efficacy of AKEEGA with AAP in patients with BRCA1/2-altered mCRPC (n=225) in a MAGNITUDE post hoc analysis, adjusting for imbalances in baseline characteristics using IPTW analysis. Time-to-event outcome analyses were evaluated and MVA was conducted based on prespecified prognostic variables of OS in mCRPC. PSA outcomes using data from the final analysis are described in Table: Unadjusted and Adjusted Time to PSA Progression.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 18 June 2025. Summarized in this response are relevant data limited to the phase 3 MAGNITUDE study in patients with mCRPC.