FDA Grants Approval to Niraparib and Abiraterone Acetate Plus Prednisone for BRCA2-Mutated Metastatic Castration-Sensitive Prostate Cancer
Key Clinical Takeaways:
- Design/Population: The AMPLITUDE trial was a randomized, double-blind study of 696 patients with HRR-mutated mCSPC comparing niraparib plus AAP versus placebo plus AAP, with FDA approval centered on the BRCA2-mutated subgroup.
- Key Outcomes: Niraparib plus AAP significantly improved rPFS, with the strongest benefit in BRCA2-mutated patients (HR 0.46; median rPFS not estimable vs 26 months), while non-BRCA2 patients saw minimal effect, and safety reflected expected PARP and AAP toxicities.
- Clinical Relevance: The results establish a meaningful new targeted therapy option for BRCA2-mutated mCSPC, highlight the importance of genomic testing, and underscore the need for careful monitoring of known treatment-related risks.
On December 12, 2025, the US Food and Drug Administration (FDA) granted approval to niraparib and abiraterone acetate ith prednisone for adults with deleterious or suspected deleterious BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC), as assessed by an FDA-approved test.
The AMPLITUDE randomized, double-blind trial, conducted in 696 patients with homologous recombination repair (HRR) gene-mutated (HRRm) mCSPC, served to demonstrate the efficacy of the treatment and its findings led to this approval. Patients were randomized 1:1 to receive niraparib and abiraterone acetate plus prednisone (AAP) or placebo and AAP. All patients also received continued androgen deprivation therapy. The study’s primary efficacy outcome measure was investigator-assessed radiographic progression-free survival (rPFS), with overall survival (OS) serving as an additional efficacy outcome.
The trial demonstrated a statistically significant improvement in rPFS for niraparib and AAP compared to placebo and AAP in the overall population of patients with HRRm. In an exploratory analysis of 323 patients with BRCA2m, the hazard ratio (HR) for rPFS was 0.46 (95% confidence interval [CI], 0.32 to 0.66) with median rPFS not estimable [NE] (95% CI, 41 to NE) for niraparib and AAP and 26 months (95% CI, 18 to 28) for placebo and AAP. In an exploratory analysis conducted among 373 patients with non-BRCA2m, the HR for rPFS was 0.88 (95% CI, 0.63 to 1.24), indicating that the overall improvement was primarily attributed to the results seen in patients with BRCA2m.
In terms of safety, at the first interim analysis for OS, 91 deaths had occurred in the BRCA2m population, including 36 (22%) on the niraparib and AAP arm and 55 (34%) on the placebo and AAP arm. The prescribing information includes warnings and precautions for myelodysplastic syndrome(MDS)/acute myeloid leukemia (AML); myelosuppression; hypokalemia; fluid retention, and cardiovascular adverse reactions; hepatoxicity; adrenocortical insufficiency; hypoglycemia; increased fractures and mortality in combination with radium Ra 223 dichloride; posterior reversible encephalopathy syndrome; and embryo-fetal toxicity.
Source:
US Food and Drug Administration. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancerAccessed December 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-and-abiraterone-acetate-plus-prednisone-brca2-mutated-metastatic-castration
