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Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial

Chi KN 1 , Sandhu S 2 , Smith MR 3 , Attard G 4 , Saad M 5 , Olmos D 6 Show all authors , Castro E 7 , Roubaud G 8 , Pereira de Santana Gomes AJ 9 , Small EJ 10 , Rathkopf DE 11 , Gurney H 12 , Jung W 13 , Mason GE 14 , Dibaj S 15 , Wu D 16 , Diorio B 17 , Urtishak K 14 , Del Corral A 18 , Francis P 19 , Kim W 16 , Efstathiou E 20

Affiliations 

  • 1 University of British Columbia, BC Cancer-Vancouver Center, Vancouver, Canada. Electronic address: kchi@bccancer.bc.ca
  • 2 Peter MacCallum Cancer Center, Melbourne, Australia; University of Melbourne, Melbourne, Australia
  • 3 Massachusetts General Hospital Cancer Center, Boston, USA; Harvard Medical School, Boston, USA
  • 4 University College London Cancer Institute, London, UK; University College London Hospitals, London, UK
  • 5 Department of Clinical Oncology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Department of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid
  • 7 Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
  • 8 Department of Medical Oncology, Institut Bergonié, Bordeaux, France
  • 9 Liga Norte Riograndense Contra o Câncer, Natal, Brazil
  • 10 Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco
  • 11 Memorial Sloan Kettering Cancer Center, New York, USA; Weill Cornell Medicine, New York, USA
  • 12 Macquarie University, Macquarie Park, Australia
  • 13 Keimyung University Dongsan Hospital, Daegu, South Korea
  • 14 Janssen Research & Development, LLC, Spring House
  • 15 Janssen Research & Development, LLC, San Diego
  • 16 Janssen Research & Development, LLC, Los Angeles
  • 17 Janssen Research & Development, LLC, Titusville
  • 18 Janssen Research & Development, LLC, Raritan
  • 19 Janssen Research & Development, LLC, Bridgewater
  • 20 Houston Methodist Cancer Center, Houston, USA
Ann Oncol, 2023 Sep;34(9):772-782.
PMID: 37399894 DOI: 10.1016/j.annonc.2023.06.009

Abstract

BACKGROUND: 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 AND METHODS: 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.

RESULTS: 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 of 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 of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed.

CONCLUSIONS: 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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