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 Journal Article


Authors: Chi, K. N.; Sandhu, S.; Smith, M. R.; Attard, G.; Saad, M.; Olmos, D.; Castro, E.; Roubaud, G.; Pereira de Santana Gomes, A. J.; Small, E. J.; Rathkopf, D. E.; Gurney, H.; Jung, W.; Mason, G. E.; Dibaj, S.; Wu, D.; Diorio, B.; Urtishak, K.; del Corral, A.; Francis, P.; Kim, W.; Efstathiou, E.
Article Title: 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
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. © 2023 The Authors
Keywords: controlled study; treatment outcome; genetics; prednisone; clinical trial; antineoplastic agent; randomized controlled trial; antineoplastic combined chemotherapy protocols; brca1 protein; brca2 protein; phase 3 clinical trial; abiraterone acetate; brca; brca1 protein, human; castration resistant prostate cancer; homologous recombination repair; brca2 protein, human; niraparib; recombinational dna repair; recombination repair; metastatic castration-resistant prostate cancer; humans; human; male; prostatic neoplasms, castration-resistant
Journal Title: Annals of Oncology
Volume: 34
Issue: 9
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2023-09-01
Start Page: 772
End Page: 782
Language: English
DOI: 10.1016/j.annonc.2023.06.009
PUBMED: 37399894
PROVIDER: scopus
PMCID: PMC10849465
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Dana Elizabeth Rathkopf
    273 Rathkopf