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

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Author(s)
K N ChiS SandhuM R SmithG AttardM SaadD OlmosE CastroG RoubaudA J Pereira de Santana GomesE J SmallD E RathkopfH GurneyW JungG E MasonS DibajD WuB DiorioK UrtishakA Del CorralP FrancisW KimE Efstathiou
Keimyung Author(s)
Jeong, Woon Kyung
Department
Dept. of Surgery (외과학)
Journal Title
Ann Oncol
Issued Date
2023
Volume
34
Issue
9
Keyword
BRCAabiraterone acetatehomologous recombination repairmetastatic castration-resistant prostate cancerniraparib
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.
Keimyung Author(s)(Kor)
정운경
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1569-8041
Source
https://www.sciencedirect.com/science/article/pii/S0923753423007573?via%3Dihub
DOI
10.1016/j.annonc.2023.06.009
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45171
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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