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AKEEGA®

(niraparib and abiraterone acetate)

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AKEEGA® (niraparib and abiraterone acetate)

Medical Information

AKEEGA - Use of AKEEGA in Patients with BRCA Gene Mutations

Last Updated: 12/25/2025

Summary

  • MAGNITUDE (NCT03748641) is a phase 3, randomized, double-blind, placebocontrolled, global study that evaluated the efficacy and safety of AKEEGA with prednisone compared with placebo/abiraterone acetate with prednisone (AAP) as first-line therapy in metastatic castration-resistant prostate cancer (mCRPC) for patients with certain homologous recombination repair (HRR) mutations, including BRCA1/2. The primary endpoint is radiographic progression-free survival (rPFS).1-7
    • Patients were prospectively allocated to cohort 1 or 2 based on prescreening for HRR+ or HRR- status and subsequently randomized to receive niraparib or matching placebo in combination with AAP.
    • Prespecified endpoint results for the BRCA1/2 subgroup are described in Table: Prespecified Primary and Key Secondary Endpoint Results: BRCA1/2 Subgroup.
    • At the first interim analysis (IA1)3:
      • In patients with BRCA1/2 mutations with a median follow-up of 16.7 months, a statistically significant improvement in median rPFS as assessed by blinded independent central review (BICR) was observed in the niraparib/AAP group compared to the placebo/AAP group: 16.6 months vs 10.9 months (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.36-0.79; P=0.001).
    • At the final analysis6:
      • Across all BRCA1/2 patients, after a median follow-up of 37.3 months, the median OS favored the niraparib/AAP group compared with the placebo/AAP group: 30.36 months vs 28.55 months (HR, 0.788; 95% CI, 0.554-1.120).
    • Safety analyses were not specifically reported for patients with BRCA gene mutations. A summary of treatment-emergent adverse events (TEAEs) reported in both treatment arms is described in Table: Summary of Most Common (≥10% in Either Group) TEAEs at IA2 (HRR+ Population).
    • Results have been reported from a post hoc analysis that adjusted for imbalances in baseline characteristics using inverse probability of treatment weighting (IPTW) analysis (Table: Unadjusted and Adjusted Outcomes).8,9 
    • Results from an analysis of health-related quality of life (HRQoL), pain, and tolerability which evaluated Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) score changes from baseline, have been reported.10,11
  • AMPLITUDE (NCT04497844) is an ongoing, phase 3, randomized, double-blind, placebo-controlled, multicenter, global study evaluating the efficacy and safety of AKEEGA with prednisone plus androgen deprivation therapy (ADT) compared to matching oral placebo/AAP plus ADT in patients with deleterious germline or somatic HRR gene-altered metastatic castration-sensitive prostate cancer (mCSPC), including BRCA1/2 (N=696).12-16
    • The primary endpoint of rPFS in the AKEEGA with prednisone group vs placebo/AAP group was met.
      • Median rPFS of BRCA subgroup: not estimable (NE) vs 26.0 months; HR, 0.52; 95% CI, 0.37-0.72; P<0.0001
      • Median rPFS of HRR effector subgroup: NE vs 27.6 months; HR, 0.57; 95% CI, 0.42-0.77; P=0.0003
      • Median rPFS intention-to-treat (ITT) population: NE vs 29.5 months; HR, 0.63; 95% CI, 0.49-0.80; P=0.0001
    • Safety analyses were not specifically reported for patients with BRCA subgroup. A summary of TEAEs reported in both treatment arms is shown in Table: Adverse Events.15-17
    • In the AKEEGA with prednisone vs placebo/AAP group, the most common AEs of interest were anemia (51.6% vs 23.9%) and hypertension (43.8% vs 32.5%), respectively.

CLINICAL DATA

MAGNITUDE Study

Chi et al (2023, 2025)3,5,6 and Efstathiou et al (2023)4 reported the efficacy and safety of AKEEGA with prednisone compared with placebo/AAP in mCRPC for patients with (n=423) and without (n=233) certain HRR gene mutations, including BRCA1/2 (n=225).

Study Design/Methods

  • Phase 3, randomized, double-blind, placebo-controlled, global study
  • Patients were prospectively allocated to cohort 1 or 2 based on prescreening for HRR+ or HRR- status. The HRR+ panel included ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, and PALB2 (qualified by plasma, tissue, and/or saliva/whole blood assays).
  • A third, open-label cohort (cohort 3) was added to evaluate niraparib 200 mg and abiraterone acetate 1000 mg (dual action tablet formulation) orally (PO) once daily with prednisone 5 mg twice daily.
  • Preplanned sensitivity analyses for OS included a proportional-hazards Cox regression multivariate analysis (MVA) adjusted for externally validated, clinically relevant baseline prognostic factors, inverse probability of censoring weighting (IPCW) adjusted for imbalances in the use of subsequent therapies, and censoring for death due to coronavirus disease 2019 (COVID-19).
  • The study design is presented in Figure: MAGNITUDE Study Design.

MAGNITUDE Study Design1-3,18-20

A screenshot of a computer screen AI-generated content may be incorrect.

Abbreviations: 1L, first-line; AA, abiraterone acetate; AAP, abiraterone acetate with prednisone; AML, acute myeloid leukemia; AR, androgen receptor; BM, biomarker; BPI-SF, Brief Pain Inventory-Short Form; CT, computed tomography; DAT, dual action tablet; ECOG PS, Eastern Cooperative Oncology Group performance status; EQ-5D-5L, European quality of life five-dimension five-level; FACT-P, functional assessment of cancer therapy-prostate; GnRHa, gonadotropin-releasing hormone analog; HRQoL, health-related quality of life; HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; MDS, myelodysplastic syndrome; MRI, magnetic resonance imaging; NIRA, niraparib; nmCRPC, nonmetastatic castration-resistant prostate cancer; ORR, objective response rate; OS, overall survival; PARPi, poly ADP-ribose polymerase inhibitor; PBO, placebo; PFS2, progression-free survival on first subsequent therapy; PO, orally; PROs, patient-reported outcomes; PRO-CTCAE, PRO version of the common terminology criteria for adverse events; PSA, prostate-specific antigen; R, randomization; rPFS, radiographic progression-free survival; TCC, time to cytotoxic chemotherapy; TSP, time to symptomatic progression; TPSA, time to PSA progression.
aNovel second-generation AR-targeted therapy such as apalutamide, enzalutamide, or darolutamide; taxane-based chemotherapy; or >4 months of AAP before R.
bOpen-label cohort.
cPROs were collected to evaluate pain, prostate cancer symptoms, treatment-related tolerability, and overall HRQoL. Disease-related symptoms were assessed with the BPI-SF and FACT-P questionnaires. Treatment-related tolerability and experiences were assessed with select items from the PRO-CTCAE and a single item from the FACT-P regarding “side effect bother.” Overall HRQoL was to be measured with FACT-P and EQ-5D-5L.

Results

Patient Characteristics
  • Baseline characteristics were broadly comparable between treatment arms in the HRR+ cohort; however, rates of visceral metastases, bone metastases, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 1 were imbalanced to the disadvantage of the niraparib/AAP group.3
  • Select baseline patient characteristics in the BRCA1/2 subgroup are shown in Table: Select Baseline Patient Characteristics: BRCA1/2 Subgroup.

Select Baseline Patient Characteristics: BRCA1/2 Subgroup3,5,6 
NIRA/AAP
(n=113)
PBO/AAP
(n=112)
Median age, years (range)
67 (45-100)
68 (43-88)
Race, n (%)
   American Indian/Alaska native
0
0
   Asian
18 (15.9)
20 (17.9)
   Black/African American
3 (2.7)
0
   White
78 (69.0)
84 (75.0)
   Unknown
14 (12.4)
8 (7.1)
ECOG PS 0, n (%)
69 (61.1)
80 (71.4)
ECOG PS 1, n (%)
44 (38.9)
32 (28.6)
Bone metastases, n (%)
99 (87.6)
93 (83.0)
Visceral metastases, n (%)
26 (23.0)
22 (19.6)
   Liver
10 (8.8)
7 (6.3)
   Lung
12 (10.6)
11 (9.8)
Median PSA at study entry, µg/L (range)
18.7 (0.1-2225.8)
14.1 (0.1-4400.0)
Prior taxane-based chemotherapy for nmCRPC/mCSPC, n (%)
26 (23.0)
29 (25.9)
Prior ARPI for nmCRPC/mCSPC, n (%)
6 (5.3)
5 (4.5)
Prior AAP therapy for L1 mCRPCa, n (%)
30 (26.5)
29 (25.9)
Abbreviations: AAP, abiraterone acetate plus prednisone; ARPI, androgen receptor pathway inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status; L1, first-line; mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; NIRA, niraparib; nmCRPC, nonmetastatic castration-resistant prostate cancer; PBO, placebo; PSA, prostate-specific antigen.
aPatients could have received up to 4 months of AAP before study entry.

BRCA1/2 Subgroup

Efficacy

Prespecified Primary and Key Secondary Endpoint Results: BRCA1/2 Subgroup3,5,7
NIRA/AAP
(n=113)
PBO/AAP
(n=112)
Hazard Ratio (95% CI)
P-Value
Primary endpoint at IA1a
   Median rPFS (BICR-
   assessed), months
16.6
10.9
0.53 (0.36-0.79)
0.001
Primary endpoint at IA2b
   Median rPFS (BICR-
   assessed), months
19.5
10.9
0.55 (0.39-0.78)
Nominal P=0.0007c
Key secondary endpoints at IA2
   Median TCC, months
NR
27.3
0.56 (0.35-0.90)
Nominal P=0.0152c
   Median TSP, months
NR
23.6
0.54 (0.35-0.85)
Nominal P=0.0071c
   Median OSd, months
29.3
28.6
0.88 (0.58-1.34)
Nominal P=0.5505c
Key secondary endpoints at FAe
   Median OSf, months
30.36
28.55
0.788 (0.554-1.120)
Nominal P=0.183c
   OS with MVA
-
-
0.663 (0.464-0.947)
Nominal P=0.024c
   Median TCC, months
NR
35.81
0.598 (0.387-0.924)
Nominal P=0.019c
   Median TSP, months
-
-
0.562 (0.371-0.849)
Nominal P=0.006c
Abbreviations: AAP, abiraterone acetate with prednisone; BICR, blinded independent central review; CI, confidence interval; FA, final analysis; HRR, homologous recombination repair; IA1, first interim analysis; IA2, second interim analysis; MVA, multivariate analysis; NIRA, niraparib; NR, not reached; OS, overall survival; PBO, placebo; rPFS, radiographic progression-free survival; TCC, time to cytotoxic chemotherapy; TSP, time to symptomatic progression.
aMedian follow-up: 16.7 months.
bAs rPFS was found to be statistically significant at IA1, no formal statistical testing was performed for IA2 or FA. IA2 had an additional 8.1 months of follow-up from IA1.
cThese endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.
dMedian follow-up: 24.8 months. There was a trend in stratified analysis toward improved OS with NIRA/AAP.
eMedian follow-up: 37.3 (range, 0.3-47.9) months. In the niraparib/AAP vs placebo/AAP group, median
treatment duration was 20.2 vs 15.2 months.
fFinal analysis occurred when 240/246 (97.6%) of the required number of events had accrued.
  • At the second interim analysis (IA2):
    • The prespecified IPCW analysis of OS was used to account for imbalances in subsequent use of PARP inhibitors and other life-prolonging therapies: niraparib/AAP vs placebo/AAP (HR, 0.54; 95% CI, 0.33-0.90; nominal P=0.0181).
    • The prespecified OS MVA was used to account for important prognostic factors: niraparib/AAP vs placebo/AAP (HR, 0.68; 95% CI, 0.45-1.05; nominal P=0.0793).
    • These endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.
  • At the final analysis7:
    • Results from the IPCW analysis revealed a longer OS with niraparib/AAP vs placebo/AAP in the BRCA1/2 subgroup (HR, 0.645; 95% CI, 0.415-1.002; nominal P=0.051). These endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.
    • At IA2, a prespecified sensitivity analysis, in which COVID-19-related deaths were censored, assessed the potential impact of the pandemic on OS. No COVID-19 related deaths occurred between IA2 and the final analysis. In the updated analysis with censoring of COVID-19-related deaths, the HR for OS was 0.704 (95% CI, 0.488-1.015; nominal P=0.059) in the BRCA1/2 subgroup. These endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.
    • In the niraparib/AAP group and placebo/AAP group, 48 (22.6%) and 40 (19.0%) patients were still receiving treatment, respectively. There were 53.1% of patients in the niraparib/AAP vs 76.8% of patients in the placebo/AAP group that discontinued treatment due to disease progression.
    • Subsequent treatment in patients with disease progression is summarized in Table: Subsequent Treatment (BRCA+ Subgroup).

Subsequent Treatment (BRCA+ Subgroup)7
Subsequent Treatment, n (%)
NIRA/AAP
(n=60)
PBO/AAP
(n=86)
Any subsequent therapy
42 (70.0)
74 (86.0)
PARP inhibitor
3 (5.0)a
29 (33.7)b
Chemotherapy
34 (56.7)
51 (59.3)
   Docetaxel
23 (38.3)
41 (47.7)
   Cabazitaxel
11 (18.3)
16 (18.6)
   Platinum-based chemotherapyc
9 (15.0)
8 (9.3)
   Other chemotherapyd
1 (1.7)
4 (4.7)
AR-targeted treatmente
12 (20.0)
24 (27.9)
Abbreviations: AAP, abiraterone acetate plus prednisone; ADP, adenosine diphosphate; AR, androgen receptor; NIRA, niraparib; PARP, poly ADP-ribose polymerase; PBO, placebo.
aAll Olaparib.
bOlaparib, niraparib, rucaparib, or talazoparib.
cCisplatin, carboplatin, carboplatin + cabazitaxel or etoposide or docetaxel.
dEstramustine, etoposide, mitoxantrone, vinorelbine.
eEnzalutamide, darolutamide, apalutamide, abiraterone, or bicalutamide.
Safety
  • Safety analyses were not specifically reported for patients with BRCA gene mutations in the MAGNITUDE study.
  • At IA2, a total of 211 patients in the niraparib/AAP group and 203 patients in the placebo/AAP group reported AEs, described in Table: Summary of Most Common (≥10% in Either Group) TEAEs at IA2 (HRR+ Population).5
  • The most common AEs for niraparib/AAP vs placebo/AAP, regardless of causality, were anemia, hypertension, and constipation. The most common AEs leading to dose interruption or reduction in the niraparib/AAP group were anemia, thrombocytopenia, and neutropenia.5 

Summary of Most Common (≥10% in Either Group) TEAEs at IA2 (HRR+ Population)5
NIRA/AAP
(n=212)
PBO/AAP
(n=211)
Treatment-related AEs, n (%)
165 (77.8)
121 (57.3)
Treatment-related death, n
1a
1b
AEs leading to dose reduction of any agent, %
20.3
3.8
AEs leading to dose interruption of any agent, %
49.1
27.5
AEs leading to discontinuations of any agent, %
15.1
5.7
AEs leading to death, n (%)
19 (9.0)
9 (4.3)
   COVID-19 related, %
4.7
0.9
n (%)
NIRA/AAP
(n=212)
PBO/AAP
(n=211)
All Grades
Grade 3
Grade 4
All Grades
Grade 3
Grade 4
Patients with ≥1 SAE
93 (43.9)
-
-
61 (28.9)
-
-
Any TEAEs
211 (99.5)
121 (57.1)
32 (15.1)
203 (96.2)
91 (43.1)
13 (6.2)
   Hematologic
      Anemia
106 (50.0)
61 (28.8)
3 (1.4)
48 (22.7)
18 (8.5)
0 (0.0)
      Thrombocytopenia
49 (23.1)
8 (3.8)
8 (3.8)
20 (9.5)
5 (2.4)
0 (0.0)
      Neutropenia
32 (15.1)
11 (5.2)
3 (1.4)
15 (7.1)
4 (1.9)
1 (0.5)
      Leukopenia
23 (10.8)
4 (1.9)
0 (0.0)
5 (2.4)
1 (0.5)
0 (0.0)
      Lymphopenia
22 (10.4)
8 (3.8)
1 (0.5)
4 (1.9)
1 (0.5)
1 (0.5)
   Cardiovascular
      Hypertension
70 (33.0)
33 (15.6)
0 (0.0)
47 (22.3)
26 (12.3)
0 (0.0)
      Hypokalemia
29 (13.7)
7 (3.3)
1 (0.5)
21 (10.0)
7 (3.3)
0 (0.0)
      Hyperglycemia
25 (11.8)
6 (2.8)
1 (0.5)
18 (8.5)
2 (0.9)
0 (0.0)
      Blood ALP increased
23 (10.8)
10 (4.7)
2 (0.9)
16 (7.6)
5 (2.4)
0 (0.0)
      ALT increased
11 (5.2)
0 (0.0)
0 (0.0)
22 (10.4)
10 (4.7)
0 (0.0)
   General disorders
      Fatigue
63 (29.7)
8 (3.8)
0 (0.0)
40 (19.0)
11 (5.2)
0 (0.0)
      Dyspnea
38 (17.9)
5 (2.4)
0 (0.0)
14 (6.6)
4 (1.9)
0 (0.0)
      Back pain
36 (17.0)
6 (2.8)
0 (0.0)
47 (22.3)
2 (0.9)
0 (0.0)
      Asthenia
35 (16.5)
2 (0.9)
1 (0.5)
21 (10.0)
1 (0.5)
0 (0.0)
      Arthralgia
32 (15.1)
1 (0.5)
0 (0.0)
23 (10.9)
2 (0.9)
0 (0.0)
      Dizziness
27 (12.7)
1 (0.5)
0 (0.0)
13 (6.2)
0 (0.0)
0 (0.0)
      Insomnia
24 (11.3)
0 (0.0)
0 (0.0)
8 (3.8)
0 (0.0)
0 (0.0)
      Bone pain
23 (10.8)
4 (1.9)
0 (0.0)
24 (11.4)
1 (0.5)
0 (0.0)
      Urinary tract infection
22 (10.4)
7 (3.3)
0 (0.0)
18 (8.5)
4 (1.9)
0 (0.0)
      Weight decreased
22 (10.4)
3 (1.4)
0 (0.0)
7 (3.3)
1 (0.5)
0 (0.0)
      Fall
16 (7.5)
2 (0.9)
0 (0.0)
29 (13.7)
6 (2.8)
0 (0.0)
   Gastrointestinal
      Constipation
70 (33.0)
1 (0.5)
0 (0.0)
33 (15.6)
0 (0.0)
0 (0.0)
      Nausea
52 (24.5)
1 (0.5)
0 (0.0)
31 (14.7)
1 (0.5)
0 (0.0)
      Decreased appetite
33 (15.6)
2 (0.9)
0 (0.0)
15 (7.1)
1 (0.5)
0 (0.0)
      Vomiting
31 (14.6)
2 (0.9)
0 (0.0)
16 (7.6)
2 (0.9)
0 (0.0)
Abbreviations: AAP, abiraterone acetate plus prednisone; AE, adverse event; ALP, alkaline phosphatase; ALT, alanine aminotransferase; COVID-19, coronavirus disease 2019; HRR, homologous recombination repair; IA2, second interim analysis; MI, myocardial infarction; NIRA, niraparib; PBO, placebo; SAE, severe adverse event; TEAE, treatment-emergent adverse event.
aDue to pneumonia.
bDue to acute MI.

Safety Summary: Final Analysis (HRR+ Population Cohort)6
AE, n (%)
NIRA/AAP (n=212)
PBO/AAP (n=211)
Any TEAEs
212 (100)
205 (97.2)
Related TEAEs
168 (79.2)
123 (58.3)
Grade 3-4 AEs
157 (74.1)
108 (51.2)
Serious AEs
100 (47.2)
65 (30.8)
   Related serious TEAEs
29 (13.7)
8 (3.8)
TEAEs leading to discontinuations of any agent
39 (18.4)
17 (8.1)
TEAEs leading to deatha
22 (10.4)
10 (4.7)
COVID-19 related or suspected TEAEs
10 (4.7)
2 (0.9)
AEs leading to dose interruption of NIRA/PBO
109 (51.4)
60 (28.4)
AEs leading to dose reduction of NIRA/PBO
43 (20.3)
8 (3.8)
AEs leading to discontinuations of NIRA/PBO
39 (18.4)
14 (6.6)
Abbreviations: AAP, abiraterone acetate plus prednisone; AE, adverse event; COVID-19, coronavirus disease 2019; HRR, homologous recombination repair; NIRA, niraparib; PBO, placebo; TEAE, treatment-emergent adverse event.
Note: Median treatment exposure: 20.2 months in the NIRA/AAP group and 15.2 months in the PBO/AAP group.
aMost common were COVID-19 in the NIRA/AAP arm (2.8%) and suspected COVID-19, acute myocardial infarction, and myocardial infarction in the PBO/AAP arm (0.9% each).

TEAEs of Special Interest: Final Analysis (HRR+ Population)6
AE, n (%)
NIRA/AAP
(n=212)
PBO/AAP
(n=211)
Any Grade
Grade ≥3
Any Grade
Grade ≥3
Patients with ≥1 AE of special interest
179 (84.4)
113 (53.3)
136 (64.5)
64 (30.3)
   Anemia
111 (52.4)
65 (30.7)
48 (22.7)
18 (8.5)
   Hypertension
72 (34.0)
35 (16.5)
49 (23.2)
27 (12.8)
   Thrombocytopenia
51 (24.1)
18 (8.5)
20 (9.5)
5 (2.4)
   Fluid retention/edema
36 (17.0)
2 (0.9)
30 (14.2)
0
   Hypokalemia
34 (16.0)
12 (5.7)
22 (10.4)
7 (3.3)
   Neutropenia
34 (16.0)
14 (6.6)
15 (7.1)
5 (2.4)
   Hepatotoxicity
30 (14.2)
5 (2.4)
27 (12.8)
10 (4.7)
   Arrhythmia
28 (13.2)
7 (3.3)
16 (7.6)
4 (1.9)
   Ischemic heart disease
11 (5.2)
8 (3.8)
10 (4.7)
8 (3.8)
   Cerebrovascular disorders
7 (3.3)
2 (0.9)
5 (2.4)
2 (0.9)
   Cardiac failure
6 (2.8)
4 (1.9)
4 (1.9)
1 (0.5)
   Osteoporosis including
   osteoporosis-related fractures
3 (1.4)
0
6 (2.8)
0
   Acute myeloid leukemia
0
0
1 (0.5)
1 (0.5)
   Rhabdomyolysis/myopathy
0
0
1 (0.5)
0
Abbreviations: AAP, abiraterone acetate plus prednisone; AE, adverse event; HRR, homologous recombination repair; NIRA, niraparib; PBO, placebo; TEAE, treatment-emergent adverse event.
  • Safety profiles across IA1, IA2, and the final analysis were consistent, with no new safety signals.7 

Post Hoc Analysis

Roubaud et al (2024)8,9 reported the efficacy of AKEEGA with AAP in patients with BRCA1/2-altered mCRPC (n=225) in MAGNITUDE after adjustment for imbalances in baseline characteristics. In a post hoc analysis that adjusted for imbalances in baseline characteristics using IPTW analysis, time-to-event outcome analyses were evaluated in patients with BRCA1/2-altered mCRPC. MVA was conducted based on prespecified prognostic variables of OS in mCRPC. Outcomes are described in Table: Unadjusted and Adjusted Outcomes.


Unadjusted and Adjusted Outcomes8,9
NIRA/AAP (n=113)
PBO/AAP (n=112)
Hazard Ratio (95% CI)
P-Value
rPFS, months
   Unadjusted, median (95% CI)
19.5 (15.0-28.7)
10.9 (8.3-13.7)
0.55 (0.39-0.78)
0.183
   IPTW, median (95% CI)
22.0 (16.5-28.7)
8.4 (8.2-12.7)
0.47 (0.33-0.66)
<0.001
   Multivariate analysis
-
-
0.50 (0.35-0.70)
<0.001
TCC, months
   Unadjusted, median (95% CI)
NE (31.4-NE)
28.2 (20.7-NE)
0.60 (0.39-0.92)
0.0192
   IPTW, median (95% CI)
NE (NE-NE)
25.0 (17.9-NE)
0.49 (0.32-0.76)
0.0012
   Multivariate analysis
-
-
0.48 (0.31-0.75)
0.0014
TSP, months
   Unadjusted, median (95% CI)
NE (36.2-NE)
21.7 (17.6-35.8)
0.56 (0.37-0.85)
0.0056
   IPTW, median (95% CI)
NE (36.2-NE)
21.3 (17.3-35.8)
0.49 (0.33-0.74)
0.0007
   Multivariate analysis
-
-
0.51 (0.33-0.78)
0.0017
OS, months
   Unadjusted, median (95% CI)
30.4 (27.6-NE)
28.6 (23.8-33.0)
0.79 (0.55-1.12)
0.183b
   IPTW, median (95% CI)
34.1 (28.5-NE)
27.4 (20.8-32.4)
0.65 (0.46-0.93)
0.017
   Multivariate analysis
-
-
0.66 (0.46-0.95)
0.024b
Time to PSA progression, months
   Unadjusted, median (95% CI)
20.7 (14.8-NE)
9.2 (7.4-14.7)
0.51 (0.35-0.73)
0.0002
   IPTW, median (95% CI)
22.1 (16.8-NE)
8.3 (6.5-12.9)
0.42 (0.30-0.60)
<0.0001
   Multivariate analysis
-
-
0.37 (0.25-0.53)
<0.0001
Time to treatment discontinuation, months
   Unadjusted, median (95% CI)
20.5 (16.6-22.3)
14.4 (11.3-16.6)
0.67 (0.50-0.90)
0.008
   IPTW, median (95% CI)
20.9 (16.9-23.8)
14.0 (11.0-15.9)
0.56 (0.41-0.75)
<0.001
   Multivariate analysis
-
-
0.57 (0.42-0.77)
<0.001
PFS2, months
   Unadjusted, median (95% CI)
28.7 (25.2-34.1)
23.8 (19.5-28.6)
0.72 (0.51-1.02)
0.0606
   IPTW, median (95% CI)
29.5 (27.0-NE)
22.9 (18.0-25.7)
0.58 (0.41-0.82)
0.002
   Multivariate analysis
-
-
0.64 (0.45-0.90)
0.0116
Abbreviations: AAP, abiraterone acetate plus prednisone; CI, confidence interval; IPTW, inverse probability of treatment weighting; NE, not estimable; NIRA, niraparib; OS, overall survival; PBO, placebo; PFS2, second progression-free survival; PSA, prostate-specific antigen; rPFS, radiographic progression-free survival; TCC, time to cytotoxic chemotherapy; TSP, time to symptomatic progression.
arPFS is reported using data from the second interim analysis of MAGNITUDE, and remaining outcomes are reported using data from the final analysis.
bThese endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.
Note: Unadjusted hazard ratios were calculated using a stratified model, with prior AAP and prior taxane-based chemotherapy as stratification factors.

AMPLITUDE Study

Attard et al (2025)16 reported efficacy and safety results of AKEEGA with prednisone plus ADT vs placebo/AAP plus ADT in patients with deleterious germline or somatic HRR gene-altered mCSPC (N=696).

Study Design/Methods

  • Phase 3, randomized, double-blind, placebo-controlled, multicenter, global study
  • The study design is presented in Figure: AMPLITUDE Study Design.
  • Key efficacy endpoint testing was conducted using a hierarchical graphical approach, first in the BRCA subgroup (BRCA1 or BRCA2 alterations), then HRR effector subgroup (ie, immediate effectors of HRR at DNA double-strand breaks [BRCA subgroup + BRIP1, PALB2, RAD51B, RAD54L]), and then all ITT patients (HRR effectors subgroup + CDK12, CHEK2, and FANCA).

AMPLITUDE Study Design12-14,16

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Abbreviations: AA, abiraterone acetate; AAP, abiraterone acetate plus prednisone; ADT, androgen deprivation therapy; AML, acute myeloid leukemia; ARPI, androgen receptor pathway inhibitor; BRCA, breast cancer susceptibility gene; CT, computed tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; HRR, homologous recombination repair; mCSPC, metastatic castration-sensitive prostate cancer; MDS, myelodysplastic syndrome; MRI, magnetic resonance imaging; NIRA, niraparib; PARPi, poly (adenosine diphosphate-ribose) polymerase inhibitor; PBO, placebo; PC, prostate cancer; QD, once daily; R, randomization; rPFS, radiographic progression-free survival.
aPatients with lymph node-only disease were not eligible. Metastatic disease as documented by CT, MRI, or bone scan.
bFinal dose must be received ≤3 months prior to randomization.
c≤1 course radiation or surgery for symptoms; radiation completed before randomization.
dIf completed ≥1 year before randomization.
eIncluding radiation, prostatectomy, lymph node dissection, and systemic therapies.
fBy investigator. Defined as time from randomization to date of radiographic progression or death, whichever occurred first.
gEvaluation based on adverse events and clinical lab evaluations using National Cancer Institute Common Terminology Criteria for Adverse
Events v5.0.

Results

Patient Characteristics

Select Baseline Patient and Disease Characteristics16 
Characteristics
BRCA subgroup
HRR Effector subgroup
ITT population
AKEEGA + Prednisone Group
(n=191)
PBO/AAP Group
(n=196)
AKEEGA + Prednisone Group
(n=230)
PBO/AAP Group
(n=226)
AKEEGA + Prednisone Group
(N=348)
PBO/AAP Group
(N=348)
Median age, years (range)
67
(41-88)
66
(44-92)
68
(41-88)
66
(40-92)
68
(40–88)
67
(40-92)
ECOG-PS score, n (%)
   0
133 (69.6)
130 (66.3)
162 (70.4)
147 (65.0)
242 (69.5)
218 (62.6)
   1
55 (28.8)
65 (33.2)
63 (27.4)
77 (34.1)
97 (27.9)
124 (35.6)
   2
3 (1.6)
1 (0.5)
5 (2.2)
2 (0.9)
9 (2.6)
6 (1.7)
Gleason score at initial diagnosis, n (%)
   ≤7
25 (13.1)
30 (15.3)
34 (14.8)
34 (15.0)
60 (17.2)
68 (19.5)
   >7
160 (83.8)
158 (80.6)
187 (81.3)
182 (80.5)
276 (79.3)
262 (75.3)
   Unknown
6 (3.1)
8 (4.1)
9 (3.9)
10 (4.4)
12 (3.4)
18 (5.2)
Metastatic stage at initial diagnosis, n (%)
   Non-
   metastatic
14 (7.3)
16 (8.2)
19 (8.3)
20 (8.8)
32 (9.2)
36 (10.3)
   Metastatic
167 (87.4)
175 (89.3)
200 (87.0)
201 (88.9)
301 (86.5)
302 (86.8)
   Unknown
10 (5.2)
5 (2.6)
11 (4.8)
5 (2.2)
15 (4.3)
10 (2.9)
Metastatic disease volume at start of ADT, n (%)
   High
151 (79.1)
155 (79.1)
179 (77.8)
178 (78.8)
269 (77.3)
271 (77.9)
   Low
40 (20.9)
41 (20.9)
51 (22.2)
48 (21.2)
79 (22.7)
77 (22.1)
Median time from start of ADT for metastatic disease, months (range)
2.14
(0.2-6.0)
2.32
(0.3-6.1)
2.27
(0.2-6.2)
2.30
(0.3-6.1)
2.46
(0.2-6.2)
2.30
(0.1-6.2)
Median PSA level at initial diagnosis, µg/L (range)
-
-
-
-
112.3
(0.1-17475)
101.6
(0.1-15900)
Median PSA level at baseline, µg/L (range)b
-
-
-
-
2.74
(0-8046)
3.57
(0-2703)
Single gene alterations, n (%)
   BRCA2
148 (77.5)
144 (73.5)
148 (64.3)
144 (63.7)
148 (42.5)
144 (41.4)
   CHEK2
-
-
-
-
72 (20.7)
76 (21.8)
   CDK12
-
-
-
-
28 (8.0)
28 (8.0)
   BRCA1
25 (13.1)
25 (12.8)
25 (10.9)
25 (11.1)
25 (7.2)
25 (7.2)
   FANCA
-
-
-
-
15 (4.3)
15 (4.3)
   RAD54L
-
-
12 (5.2)
6 (2.7)
12 (3.4)
6 (1.7)
   PALB2
-
-
9 (3.9)
13 (5.8)
9 (2.6)
13 (3.7)
  BRIP1
-
-
9 (3.9)
4 (1.8)
9 (2.6)
6 (1.7)
  RAD51B
-
-
4 (1.7)
5 (2.2)
4 (1.1)
5 (1.4)
Co-occurring BRCA alterationsc
18 (9.4)
27 (13.8)
18 (7.8)
27 (11.9)
18 (5.2)
27 (7.8)
   BRCA2/CHEK2
5 (2.6)
13 (6.6)
5 (2.2)
13 (5.8)
5 (1.4)
13 (3.7)
Co-occurring non-BRCA alterationsd
-
-
5 (2.2)
2 (0.9)
8 (2.3)
5 (1.4)
Abbreviations: AAP, abiraterone acetate plus prednisone; ADT, androgen deprivation therapy; BRCA, breast cancer susceptibility gene; ECOG-PS, Eastern Cooperative Oncology Group performance status; HRR, homologous recombination repair; ITT, intention-to-treat; mCSPC, metastatic castration-sensitive prostate cancer; PBO, placebo; PSA, prostate-specific antigen; RT, radiotherapy.
aPercentages may not total 100 because of rounding.bPatients were allowed to be on ongoing ADT; therefore, PSA levels were lower than at diagnosis.cNon-mutually exclusive.
dAll other co-occurring BRCA and non-BRCA alterations occurred at a frequency of <1%.
Efficacy
  • A summary of the study results is provided in Table: Primary, Secondary, and Other Endpoint Results. The median follow-up was 30.8 months (data cutoff: January 7, 2025).
  • The median duration of treatment for receiving AKEEGA plus prednisone vs placebo/AAP was 25.3 months vs 22.5 months.
  • Subgroup analyses by alteration type are summarized in Table: Subgroup Analysis by BRCA and non-BRCA Alterations.
  • The treatment effect of AKEEGA plus prednisone vs placebo/AAP on the median rPFS in the ITT population was generally consistent across several prespecified subgroups, including patients with high-volume disease at baseline (41.2 months [events/N, 100/269] vs 26.3 months [130/271]; HR, 0.65; 95% CI, 0.50-0.85) and M1 disease at diagnosis (NE [100/301] vs 27.4 months [142/302]; HR, 0.60; 95% CI, 0.47-0.78).
  • While not a prespecified analysis, there was a hazard ratio of 0.81 (95% CI, 0.56-1.18) for rPFS in patients without BRCA1/2 alterations.

Primary, Secondary, and Other Endpoint Results15,16
AKEEGA + Prednisone Group
(n=191)
PBO/AAP Group
(n=196)
AKEEGA + Prednisone Group
(n=230)
PBO/AAP Group
(n=226)
AKEEGA + Prednisone Group
(N=348)
PBO/AAP Group
(N=348)
BRCA subgroup
HRR Effector subgroup
ITT population
Primary Endpoint
Median rPFS,a months
NE
26.0
NE
27.6
NE
29.5
Number of events
57
93
71
102
113
151
HR (95% CI)
0.52 (0.37-0.72)
0.57 (0.42-0.77)
0.63 (0.49-0.80)
P-Value
<0.0001
0.0003
0.0001
Secondary Endpoints
Median time to symptomatic progression,b months
NE
NE
NE
NE
NE
NE
HR (95% CI)
0.44 (0.29-0.68)
0.49 (0.33-0.74)
0.50 (0.36-0.69)
P-Value
0.0001
0.0004
<0.0001
Median OS,b,c months
NE
NE
NE
NE
NE
NE
HR (95% CI)
0.75 (0.51-1.11)
0.81 (0.57-1.16)
0.79 (0.59-10.4)
P-Value
0.15
0.25
0.10
Median time to subsequent therapy, months
44.6
30.0
44.6
33.6
44.6
NE
HR (95% CI)
0.47 (0.33-0.66)
0.50 (0.36-0.69)
0.54 (0.41-0.70)
P-Value
Nominal P<0.0001d
Nominal P<0.0001d
Nominal P<0.0001d
Other Endpoints
Median second progression-free survival, months
NE
44.0
NE
44.0
NE
44.0
HR (95% CI)
0.59 (0.41-0.83)
0.63 (0.45-0.87)
0.66 (0.51-0.86)
P-Value
Nominal P=0.0026d
Nominal P=0.0049d
Nominal P=0.0017d
Objective response,e n/N (%)
48/63
(76.2)
53/72
(73.6)
58/76
(76.3)
58/79 (73.4)
76/106 (71.7)
81/110 (73.6)
HR (95% CI)f
1.04(0.85-1.26)
1.04(0.87-1.25)
0.97(0.83-1.15)
P-Value
0.73
0.68
0.75
Median time to PSA progression, months
NE
25.5
NE
29.0
NE
29.0
HR (95% CI)
0.41 (0.29-0.59)
0.48 (0.35-0.66)
0.50 (0.39-0.65)
P-Value
Nominal P<0.0001d
Nominal P<0.0001d
Nominal P<0.0001d
Confirmed PSA response,g %
88.5
85.7
87.0
85.8
87.6
86.2
HR (95% CI)f
1.03(0.96-1.12)
1.01 (0.94-1.09)
1.02(0.96-1.08)
P-Value
0.42
0.73
0.57
Abbreviations: AAP, abiraterone acetate plus prednisone; HRR, homologous recombination repair; HR, hazard ratio; ITT, intention-to-treat; NE, non estimable; OS, overall survival; PBO, placebo; PSA, prostate-specific antigen; rPFS, radiographic progression-free survival.
aBy investigator review. The results by blinded independent central review were similar: BRCA subgroup, HR, 0.51 (95% CI, 0.37-0.72), P<0.0001; HRR effector subgroup, HR, 0.58 (95% CI, 0.43-0.80), P=0.0006; and ITT population, HR, 0.61 (95% CI, 0.47-0.79), P=0.0001. This is the first and final analysis.
bFirst interim analysis; included in graphical approach for testing key efficacy endpoints.
cConducted when 193 patients died (n=85 in AKEEGA with prednisone group and n=108 in PBO/AAP group), which is ~50% of total needed events. First non-significant test in hierarchical graphical approach for testing key efficacy endpoints. P values provided for completeness.
dThese endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established.
eIn the ITT population, the duration of response in patients with complete or partial response was longer in the AKEEGA with prednisone group (HR, 0.55; 95% CI, 0.35-0.86; nominal P=0.008)d.fValue is relative risk.
gDefined as ≥50% decrease from baseline.

Subgroup Analysis by BRCA and non-BRCA Alterations15
Endpoints
HR (95% CI)
Events/N
AKEEGA + Prednisone
Group
PBO/AAP Group
Primary Endpoint
Median rPFS, months
   BRCA1/2
0.52 (0.37-0.72)
57/191
93/196
   CHEK2
0.65 (0.38-1.11)
24/72
32/76
   CDK12
1.01 (0.43-2.39)
13/28
10/28
   FANCA
0.76 (0.20-2.82)
4/15
5/15
   PALB2
2.41 (0.66-8.74)
6/9
4/13
   Othera
0.72 (0.20-2.66)
6/25
4/15
Secondary Endpoints
Median time to symptomatic progression, months
   BRCA1/2
0.44 (0.29-0.68)
31/191
66/196
   CHEK2
0.47 (0.21-1.05)
9/72
18/76
   CDK12
0.68 (0.28-1.62)
9/28
12/28
   FANCA
0.71 (0.12-4.27)
2/15
3/15
   PALB2
NE (NE-NE)
1/9
2/13
   Othera
1.18 (0.12-11.36)
4/25
1/15
Median OS, months
   BRCA1/2
0.75 (0.51-1.11)
44/191
61/196
   CHEK2
0.85 (0.45-1.59)
18/72
21/76
   CDK12
0.57 (0.25-1.31)
9/28
15/28
   FANCA
0.92 (0.20-4.12)
3/15
4/15
   PALB2
3.30 (0.52-21.21)
3/9
2/13
   Othera
0.79 (0.18-3.36)
5/25
3/15
Abbreviations: AAP, abiraterone acetate plus prednisone; HR, hazard ratio; NE, non estimable; OS, overall survival; PBO, placebo; rPFS, radiographic progression-free survival.
Note: Non-BRCA subgroups were not statistically powered for formal testing in this exploratory analysis. Hazard ratios were stratified by disease volume (high vs low).
aRAD54L, BRIP1, RAD51B.
Safety
  • In the AMPLITUDE study, safety analyses were not specifically reported for patients in the BRCA subgroup.
  • A summary of AEs reported in the safety population is shown in Table: Adverse Events.
    • In the AKEEGA with prednisone vs placebo/AAP group, the most common AEs of interest were anemia (51.6% vs 23.9%) and hypertension (43.8% vs 32.5%), respectively.

Adverse Events15-17
AE, n (%)
AKEEGA + Prednisone Groupa
(n=347)c
PBO/AAP Groupb
(n=348)
Any Grade
Grade 3-4
Any Grade
Grade 3-4
Any AE
346 (99.7)
261 (75.2)
341 (98.0)
205 (58.9)
Serious AEs
136 (39.2)
-
96 (27.6)
-
AEs leading to treatment discontinuationd
51 (14.7)e
-
36 (10.3)
-
TEAEs leading to dose reduction
76 (21.9)
-
24 (6.9)
-
TEAEs leading to dose interruption
232 (66.9)
-
147 (42.4)
-
AEs leading to death
14 (4.0)f
-
7 (2.0)
-
TEAEs of interestg
Patients with ≥1 AE of interest
306 (88)
217 (63)
261 (75)
132 (38)
Constipation
122 (35.2)
-
57 (16.4)
1 (0.3)
Nausea
107 (30.8)
-
50 (14.4)
-
Fatigue
91 (26.2)
7 (2.0)
64 (18.4)
4 (1.1)
Arthraliga
73 (21.0)
2 (0.6)
74 (21.3)
6 (1.7)
Hematologic
   Anemiah
179 (51.6)
101 (29.1)
83 (23.9)
16 (4.6)
   Neutropenia
76 (21.9)
33 (9.5)
28 (8.0)
7 (2.0)
   Thrombocytopenia
66 (19.0)
24 (6.9)
20 (5.7)
1 (0.3)
   MDS
1 (<1)
1 (<1)
0
0
Cardiovascular
   Hypertension
152 (43.8)
92 (26.5)
113 (32.5)
64 (18.4)
   Arrhythmia
68 (20)
19 (5)
28 (8)
11 (3)
   Cardiac failure
20 (6)
9 (3)
6 (2)
4 (1)
Others
   Hypokalemia
90 (25.9)
40 (11.5)
70 (20.1)
38 (10.9)
   Hepatotoxicity
46 (13)
8 (2)
71 (20)
19 (5)
Abbreviations: AAP, abiraterone acetate plus prednisone; AE, adverse event; COVID-19, coronavirus 2019; MDS, myelodysplastic syndrome; NIRA, niraparib; PBO, placebo; TEAE, treatment-emergent adverse event.
aMedian treatment duration: 25.3 months.
bMedian treatment duration: 22.5 months.
cOne randomized patient never received study drug.
dAn AE was counted as leading to discontinuation of study treatment if it led to withdrawal of NIRA/PBO or AA/PBO or prednisone. The most common in AKEEGA + prednisone vs PBO/AAP were as follows, respectively: anemia (n=8 [2.3%] vs n=2 [0.6%]), asthenia (n=4 [1.2%] vs n=3 [0.9%]), sudden death (n=3 [0.9%] vs n=1 [0.3%]), alanine aminotransferase increased (n=1 [0.3%] vs n=5 [1.4%]), aspartate aminotransferase increased (n=1 [0.3%] vs n=4 [1.1%]), hypokalemia (0 vs n=3 [0.9%]), and spinal cord compression (0 vs n=3 [0.9%]).
eIncluded one case of MDS in a patient with a CHEK2 germline mutation.
fIncluded 4 cases of respiratory infection, including 2 attributed as related to COVID-19, 4 attributed to cardiac causes, 3 classified as sudden death, and 1 each of sepsis, subdural hematoma, and multiorgan dysfunction syndrome.
gPatients were counted only once for any given event, regardless of the number of times they actually experienced the event. The event experienced by the patient with the worst toxicity grade was used. If a patient had missing toxicity for a specific AE, the patient was only counted in the total column for the AE. hRequired ≥1 transfusion in the AKEEGA + prednisone vs PBO/AAP groups, respectively: 87 (25.1%) with median of 2 (range: 1-5) vs 13 (3.7%) with median of 2 (range: 1-3).

literature search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 02 September 2025. Summarized in this response are relevant data limited to the phase 3 MAGNITUDE and AMPLITUDE studies in patients with mCRPC and mCSPC, respectively.

References

Show
1 Janssen Research & Development, LLC. A study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for treatment of participants with metastatic prostate cancer (MAGNITUDE). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 September 02]. Available from: https://clinicaltrials.gov/show/NCT03748641 NLM Identifier: NCT03748641.  
2 Chi KN, Rathkopf D, Attard G. A phase 3 randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (MAGNITUDE). Poster presented at: American Society of Clinical Oncology (ASCO) Scientific Program; May 29-31, 2020; Virtual.  
3 Chi KN, Rathkopf D, Smith MR, et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-3351.  
4 Efstathiou E, Smith MR, Sandhu S, et al. Niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: second interim analysis of MAGNITUDE. Poster presented at: American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA.  
5 Chi KN, Sandhu S, Smith MR, et al. 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. Ann Oncol. 2023;34(9):772-782.  
6 Chi KN, Castro E, Attard G, et al. Niraparib and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: final overall survival analysis for the phase 3 MAGNITUDE trial. Eur Urol Oncol. 2025;8(4):986-998.  
7 Chi KN, Castro E, Attard G, et al. Niraparib (NIRA) with abiraterone acetate plus prednisone (AAP) as first-line (1L) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: three-year update and final analysis of MAGNITUDE. Oral Presentation presented at: European Society of Medical Oncology (ESMO) Congress; October 20-24, 2023; Madrid, Spain.  
8 Roubaud G, Attard G, Boegemann M, et al. Adjustment for imbalances in baseline characteristics in the MAGNITUDE phase 3 study confirms the clinical benefit of niraparib in combination with abiraterone acetate plus prednisone in patients with metastatic prostate cancer. Eur J Cancer. 2024;209:114183.  
9 Roubaud G, Attard G, Boegemann M, et al. Supplement to: Adjustment for imbalances in baseline characteristics in the MAGNITUDE phase 3 study confirms the clinical benefit of niraparib in combination with abiraterone acetate plus prednisone in patients with metastatic prostate cancer. Eur J Cancer. 2024;209:114183.  
10 Rathkopf D, Roubaud G, Chi KN, et al. Health-related quality of life and pain in the MAGNITUDE study of niraparib with abiraterone acetate and prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL and Virtual.  
11 Rathkopf DE, Roubaud G, Chi KN, et al. Patient-reported outcomes for patients with metastatic castration-resistant prostate cancer and BRCA1/2 gene alterations: final analysis from the randomized phase 3 MAGNITUDE trial. Eur Urol. 2025;88(4):359-369.  
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13 Janssen Research & Development, LLC. A study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for the treatment of participants with deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-sensitive prostate cancer (mCSPC) (AMPLITUDE). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 September 02]. Available from: https://clinicaltrials.gov/show/NCT04497844 NLM Identifier: NCT04497844.  
14 Rathkopf DE, Chi KN, Olmos D, et al. AMPLITUDE: niraparib and abiraterone acetate plus prednisone to treat patients with metastatic castration-sensitive prostate cancer and deleterious germline or somatic homologous recombination repair gene alterations. Poster presented at: 23rd Annual Meeting of the Society of Urologic Oncology (SUO); November 30-December 2, 2022; San Diego, CA.  
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16 Attard G, Agarwal N, Graff JN, et al. Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial. [Published online ahead of print October 07, 2025]. Nat Med. doi:10.1038/s41591-025-03961-8.  
17 Attard G, Agarwal N, Graff JN, et al. Supplement to: Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial. [published online ahead of print October 07, 2025]. Nat Med. doi:10.1038/s41591-025-03961-8.  
18 Chi KN, Rathkopf DE, Smith MR, et al. Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Oral Presentation presented at: American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 17-19, 2022; San Francisco, CA.  
19 Chi KN, Rathkopf D, Smith MR, et al. Protocol for: Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-3351.  
20 Chi KN, Rathkopf D, Smith MR, et al. Supplement to: Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-3351.