FDA Approves Niraparib/Abiraterone Combo for BRCA2-Mutated mCSPC

The FDA has approved the fixed-dose combination of niraparib and abiraterone acetate (Akeega) plus prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC).

This approval restricts the use of the combination therapy specifically to patients with BRCA2 mutations, as identified by an FDA-approved test. The decision was based on results from the phase 3 AMPLITUDE trial (NCT04497844), which demonstrated a statistically significant improvement in radiographic progression-free survival (rPFS) for this specific subgroup.

Clinical Efficacy Data

The AMPLITUDE trial was a randomized, double-blind, placebo-controlled study evaluating the efficacy of the combination in patients with deleterious germline or somatic homologous recombination repair (HRR) gene-mutated mCSPC. Patients were randomized 1:1 to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 5 mg daily, or placebo and abiraterone acetate plus prednisone daily. All patients also received androgen deprivation therapy (ADT).^1,2

In the subgroup of patients with BRCA2 mutations (n = 323), the median rPFS was not estimable (NE; 95% CI, 41–NE) in the investigational arm, compared with 26 months (95% CI, 18-28) in the placebo arm. This corresponded to a hazard ratio (HR) of 0.46 (95% CI, 0.32–0.66), indicating a 54% reduction in the risk of radiographic progression or death.

While the trial showed an rPFS advantage in the overall intention-to-treat population, exploratory analyses revealed that the benefit was primarily driven by the BRCA2-mutated subgroup. In patients without BRCA2 mutations, the HR for rPFS was 0.88 (95% CI, 0.63–1.24), supporting the FDA's decision to limit the indication to the BRCA2 population.

An interim analysis of overall survival (OS) showed a trend favoring the niraparib arm, with 36 deaths (22%) occurring in the BRCA2-mutated group treated with the combination, vs 55 deaths (34%) in the control group.

Safety and Administration

The recommended dose for this indication is 200 mg niraparib and 1000 mg abiraterone acetate (administered as 2 tablets) orally once daily, in combination with 5 mg prednisone daily. Treatment should continue until disease progression or unacceptable toxicity. Patients must also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or have had a bilateral orchiectomy.

Common adverse reactions (≥20%) reported in clinical trials include musculoskeletal pain, fatigue, constipation, hypertension, and nausea. Laboratory abnormalities such as decreased hemoglobin, lymphocytes, white blood cells, and platelets were also frequently observed.

The prescribing information includes warnings for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, hypokalemia, fluid retention, and hepatotoxicity.

Clinical Context

This approval marks an expansion of the therapeutic landscape for PARP inhibitors in prostate cancer, moving their use into the hormone-sensitive setting for select patients. The combination of niraparib and abiraterone acetate plus prednisone (10 mg) was previously approved in August 2023 for BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), based on the MAGNITUDE trial.

REFERENCES

1. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. News release. U.S. Food and Drug Administration. December 12, 2025. Accessed December 12, 2025. https://tinyurl.com/3zc9j6b8

2. Attard G, Agarwal N, Graff J, et al. Phase 3 AMPLITUDE trial: niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes. J Clin Oncol. 2025;43 (suppl 17):LBA5006. doi:10.1200/JCO.2025.43.17_suppl.LBA5006