Niraparib and Abiraterone Acetate plus Prednisone in Metastatic Castration-resistant Prostate Cancer: Final Overall Survival Analysis for the Phase 3 MAGNITUDE Trial
- Author(s)
- Chi, KN; Castro, E; Attard, G; Smith, MR; Sandhu, S; Efstathiou, E; Roubaud, G; Small, EJ; de Santana Gomes, AP; Rathkopf, DE; Saad, M; Gurney, H; Jung, W; Kim, W; Dibaj, S; Wu, D; Zhang, J; Lopez-Gitlitz, A; Francis, P; Olmos, D;
- Journal Title
- European Urology Oncology
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND AND OBJECTIVE: The phase 3 MAGNITUDE trial previously met its primary endpoint of an improvement in radiographic progression-free survival with niraparib + abiraterone acetate and prednisone (AAP) versus placebo + AAP in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in genes involved in DNA homologous recombination repair (HRR(+)), particularly in BRCA1/2. METHODS: Patients were prospectively screened for HRR alterations and randomized 1:1 to niraparib + AAP (n = 212) or placebo + AAP (n = 211). We report results from the prespecified, event-driven, final analysis of secondary efficacy endpoints. KEY FINDINGS AND LIMITATIONS: Final analysis at median follow-up of 37.3 mo revealed no difference in overall survival (OS) between niraparib + AAP and placebo + AAP in the HRR(+) population (hazard ratio [HR] 0.931, 95% confidence interval [CI] 0.720-1.203; p = 0.585) or the subgroup with BRCA1/2 alterations (HR 0.788, 95% CI 0.554-1.120; nominal p = 0.183). Prespecified multivariate analyses adjusted for baseline prognostic factors showed a trend toward longer OS with niraparib + AAP over placebo + AAP in the HRR(+) population (HR 0.785, 95% CI 0.606-1.016; nominal p = 0.066) and the BRCA1/2 subgroup (HR 0.663, 95% CI 0.464-0.947; nominal p = 0.024). Niraparib + AAP led to a statistically significant, clinically meaningful improvement in time to symptomatic progression in both the HRR(+) population (HR 0.547, 95% CI 0.396-0.754; p = 0.006) and the BRCA1/2 subgroup (HR 0.562, 95% CI 0.371-0.849; nominal p = 0.006), and a clinically meaningful improvement in time to cytotoxic chemotherapy in the HRR(+) population (HR 0.688, 95% CI 0.499-0.950; p = 0.022) and the BRCA1/2 subgroup (HR 0.598, 95% CI 0.387-0.924; nominal p = 0.019) in comparison to placebo + AAP. The niraparib + AAP safety profile remains unchanged at longer follow-up; adverse events were primarily hematologic and manageable. CONCLUSIONS AND CLINICAL IMPLICATIONS: The MAGNITUDE final analysis showed that patients with HRR(+) mCRPC, including those with the approved indication of BRCA-altered mCRPC, generally continue to benefit from first-line treatment with niraparib + AAP in comparison to placebo + AAP.
- Keywords
- Clinical trial; Niraparib; Prostate cancer
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.euo.2025.04.012
- Open Access at Publisher's Site
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Creation Date: 2025-05-27 04:30:46
Last Modified: 2025-05-27 04:31:03