Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2).
Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1:1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints (time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival [OS]) were assessed.
Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n=113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival (rPFS; blinded independent central review; median rPFS, 19.5 versus 10.9 months; hazard ratio [HR]=0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P=0.0007) consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population (HR=0.76 [95% CI 0.60-0.97]; nominal P=0.0280; median follow-up, 26.8 months). Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR=0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies demonstrated an HR=0.54 (95% CI 0.33-0.90; nominal P=0.0181). No new safety signals were observed.
MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.
Annals of oncology : official journal of the European Society for Medical Oncology. 2023 Jul 01 [Epub ahead of print]
K N Chi, S Sandhu, M R Smith, G Attard, M Saad, D Olmos, E Castro, G Roubaud, A J Pereira de Santana Gomes, E J Small, D E Rathkopf, H Gurney, W Jung, G E Mason, S Dibaj, D Wu, B Diorio, K Urtishak, A Del Corral, P Francis, W Kim, E Efstathiou
University of British Columbia, BC Cancer - Vancouver Center, Vancouver, BC, Canada;. Electronic address: ., Peter MacCallum Cancer Center and the University of Melbourne, Melbourne, VIC, Australia., Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, USA., University College London Cancer Institute and University College London Hospitals, London, UK., Department of Clinical Oncology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Department of Medical Oncology, Institut Bergonié, Bordeaux, France., Liga Norte Riograndense Contra o Câncer, Natal, Brazil., Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, USA., Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, USA., Macquarie University, Macquarie Park, NSW, Australia., Keimyung University Dongsan Hospital, Dalseo-gu, Daegu, South Korea., Janssen Research & Development, LLC, Spring House, USA., Janssen Research & Development, LLC, San Diego, USA., Janssen Research & Development, LLC, Los Angeles, USA., Janssen Research & Development, LLC, Titusville, USA., Janssen Research & Development, LLC, Raritan, USA., Janssen Research & Development, LLC, Bridgewater, USA., Houston Methodist Cancer Center, Houston, USA.