FDA Approves Niraparib/Abiraterone Acetate Plus Prednisone for BRCA2+ mCSPC

The FDA has approved niraparib and abiraterone acetate (Akeega) in combination with prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer, as determined by an FDA-approved test.

The regulatory decision was supported by data from the phase 3 AMPLITUDE trial (NCT04497844). Findings from an exploratory analysis showed that patients harboring BRCA2 mutations treated with niraparib and abiraterone acetate plus prednisone (n = 162) experienced a median radiographic progression-free survival (rPFS) that was not estimable (NE; 95% CI, 41-NE) compared with 26 months (95% CI, 18-28) for those given placebo and abiraterone acetate (n = 161; HR, 0.46; 95% CI, 0.32-0.66).

Notably, the rPFS advantage in the niraparib arm was observed in the overall trial population. However, an exploratory analysis revealed that the rPFS benefit did not translate to those without BRCA2 mutations (n = 373; HR, 0.88; 95% CI, 0.63-1.24).

What was the design of the AMPLITUDE trial?

The double-blind, placebo-controlled, multicohort, multicenter study enrolled patients with homologous recombination repair (HRR) gene–mutated (HRRm) mCSPC (n = 696).2 Participants were randomly assigned 1:1 to receive 200 mg of niraparib plus 1000 mg of abiraterone acetate (n = 348) or placebo paired with abiraterone acetate (n = 348).

All patients were given prednisone at a daily dose of 5 mg and had received androgen deprivation therapy more than 2 weeks before randomization. They were stratified by HRR gene alteration (BRCA2 vs CDK12 vs all other pathogenic alterations, previous use of docetaxel (yes vs no), and disease volume at screening (high vs low).

Of the 696 patients, 323 had the BRCA2 gene mutation. In this group, the median patient age was 66 years (range, 41-92). More than half were White (68%) and had an ECOG performance status of 0 (68%). Moreover, 16% of patients previously received docetaxel, and 11% had prior exposure to abiraterone acetate for up to 45 days for mCSPC. Additionally, bone-only and visceral metastases were reported in 40% and 15% of patients, respectively. Moreover, 10% of patients had BRCA2 mutations as well as mutations in other HRR genes.

The primary end point was rPFS by by investigator-assessed radiographic progression by bone scan or soft tissue lesions by CT or MRI, or death. Additional key efficacy outcome measures were overall survival (OS) and time to symptomatic progression (TSP).

What was the OS and TSP with niraparib and abiraterone acetate plus prednisone?

Ninety-one deaths were reported in the BRCA2-mutated population at the time of the first interim analysis; 22% were in the niraparib/abiraterone acetate and prednisone arm, and 34% were in the placebo/abiraterone acetate arm.

Additionally, niraparib and abiraterone with prednisone led to a delay in TSP (HR, 0.41; 95% CI, 0.26-0.65).

What was the safety profile of niraparib and abiraterone acetate with prednisone in this population?

The median duration of exposure for niraparib and abiraterone acetate with prednisone was 26 months (range, 0-48). Dose reductions or interruptions were required in 67% and 25% of patients, respectively; serious toxicities were experienced by 36% of patients. Thirteen percent of patients had an adverse effect (AE) that led to permanent discontinuation of any component of the combination regimen.

The most common AEs reported in those with BRCA2-mutated CSPC who received niraparib and abiraterone acetate with prednisone in the study were hypertension (all grade, 51%; grade 3/4, 31%), musculoskeletal pain (45%; 6%), constipation (41%; 0%), fatigue (39%l 4.3%), nausea (30%; 0%), respiratory tract infection (23%; 0.6%), and arrhythmia (23%; 3.7%).

Other clinically relevant toxicities that were experienced by up to 20% of patients who received the regimen included hot flush (18%), vomiting (17%), dizziness (17%), abdominal pain (15%), weight decreased (14%), diarrhea (14%), decreased appetite (12%), headache (12%), hemorrhage (12%), dyspnea (10%), urinary tract infection (8%), pneumonia (7%), osteoporosis (4.9%), rash (3.7%), cardiac failure (3.1%), ischemic heart disease (4.9%), acute kidney injury (2.5%), pulmonary embolism (2.5%), and urosepsis (0.6%).

The most frequently experienced select laboratory abnormalities that worsened from baseline in those who received the regimen were decreased hemoglobin (all grade, 74%; grade 3/4, 39%), decreased lymphocyte count (59%; 20%), decreased platelet count (41%; 4.9%), decreased potassium (38%; 9%), increased creatinine (30%; 1.3%), increased alkaline phosphotase (28%; 0.6%), increased aspartate aminotransferase (28%; 0.6%), increased aspartate aminotransferase (24%; 1.3%), and increased blood bilirubin (22%; 0%).

References

1. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. FDA. December 12, 2025. Accessed December 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-and-abiraterone-acetate-plus-prednisone-brca2-mutated-metastatic-castration
2. Akeega. Prescribing information.Janssen Biotech, Inc; 2025. Accessed December 12, 2025. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/AKEEGA-pi.pdf