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
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
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.
| Errataetall: |
CommentIn: Ann Oncol. 2023 Sep;34(9):729-731. - PMID 37406813 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 34(2023), 9 vom: 24. Sept., Seite 772-782 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chi, K N [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.08.2023 Date Revised 10.02.2024 published: Print-Electronic CommentIn: Ann Oncol. 2023 Sep;34(9):729-731. - PMID 37406813 Citation Status MEDLINE |
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| doi: |
10.1016/j.annonc.2023.06.009 |
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| PPN (Katalog-ID): |
NLM359010954 |
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| 100 | 1 | |a Chi, K N |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations |b second interim analysis of the randomized phase III MAGNITUDE trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 22.08.2023 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Ann Oncol. 2023 Sep;34(9):729-731. - PMID 37406813 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BRCA | |
| 650 | 4 | |a abiraterone acetate | |
| 650 | 4 | |a homologous recombination repair | |
| 650 | 4 | |a metastatic castration-resistant prostate cancer | |
| 650 | 4 | |a niraparib | |
| 650 | 7 | |a Abiraterone Acetate |2 NLM | |
| 650 | 7 | |a EM5OCB9YJ6 |2 NLM | |
| 650 | 7 | |a Prednisone |2 NLM | |
| 650 | 7 | |a VB0R961HZT |2 NLM | |
| 650 | 7 | |a BRCA1 protein, human |2 NLM | |
| 650 | 7 | |a niraparib |2 NLM | |
| 650 | 7 | |a HMC2H89N35 |2 NLM | |
| 650 | 7 | |a BRCA1 Protein |2 NLM | |
| 650 | 7 | |a BRCA2 protein, human |2 NLM | |
| 650 | 7 | |a BRCA2 Protein |2 NLM | |
| 700 | 1 | |a Sandhu, S |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, M R |e verfasserin |4 aut | |
| 700 | 1 | |a Attard, G |e verfasserin |4 aut | |
| 700 | 1 | |a Saad, M |e verfasserin |4 aut | |
| 700 | 1 | |a Olmos, D |e verfasserin |4 aut | |
| 700 | 1 | |a Castro, E |e verfasserin |4 aut | |
| 700 | 1 | |a Roubaud, G |e verfasserin |4 aut | |
| 700 | 1 | |a Pereira de Santana Gomes, A J |e verfasserin |4 aut | |
| 700 | 1 | |a Small, E J |e verfasserin |4 aut | |
| 700 | 1 | |a Rathkopf, D E |e verfasserin |4 aut | |
| 700 | 1 | |a Gurney, H |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, W |e verfasserin |4 aut | |
| 700 | 1 | |a Mason, G E |e verfasserin |4 aut | |
| 700 | 1 | |a Dibaj, S |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, D |e verfasserin |4 aut | |
| 700 | 1 | |a Diorio, B |e verfasserin |4 aut | |
| 700 | 1 | |a Urtishak, K |e verfasserin |4 aut | |
| 700 | 1 | |a Del Corral, A |e verfasserin |4 aut | |
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| 700 | 1 | |a Kim, W |e verfasserin |4 aut | |
| 700 | 1 | |a Efstathiou, E |e verfasserin |4 aut | |
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