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.
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.
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.
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.
European urology oncology. 2025 May 05 [Epub ahead of print]
Kim N Chi, Elena Castro, Gert Attard, Matthew R Smith, Shahneen Sandhu, Eleni Efstathiou, Guilhem Roubaud, Eric J Small, Andrea Pereira de Santana Gomes, Dana E Rathkopf, Marniza Saad, Howard Gurney, Wonho Jung, Won Kim, Shiva Dibaj, Daphne Wu, Jenny Zhang, Angela Lopez-Gitlitz, Peter Francis, David Olmos
BC Cancer-Vancouver, University of British Columbia, Vancouver, Canada. Electronic address: ., Department of Medical Oncology, Hospital Universitario 12 de Octubre. Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain., University College London Cancer Institute and University College London Hospital, London, UK., Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA., Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia., Houston Methodist Cancer Center, Houston, TX, USA., Department of Medical Oncology, Institut Bergonié, Bordeaux, France., Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, USA., Liga Norte Riograndense Contra o Câncer, Natal, Brazil., Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY, USA., Department of Clinical Oncology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia., Macquarie University, Macquarie Park, Australia., Keimyung University Dongsan Hospital, Daegu, South Korea., Johnson & Johnson, Los Angeles, CA, USA., Johnson & Johnson, San Diego, CA, USA., Johnson & Johnson, Bridgewater, NJ, USA.