FDA approves niraparib plus abiraterone acetate with prednisone for BRCA2+ mCSPC

On December 12, 2025, the FDA approved the combination of niraparib and abiraterone acetate (Akeega) with prednisone (AAP) for adult patients with deleterious or suspected deleterious BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC).¹

The approval was supported by findings from the phase 3 AMPLITUDE trial (NCT04497844), which randomly assigned 696 patients 1:1 to receive abiraterone plus AAP (n = 348) or placebo plus AAP (n = 348). Overall, the trial demonstrated that adding niraparib to AAP significantly improved radiographic progression-free survival (rPFS) vs placebo and AAP in patients with mCSPC harboring homologous recombination repair (HRR) gene alterations.²

An exploratory analysis of the data was conducted in 323 patients with BRCA2-mutated mCSPC. In these patients, the hazard ratio for rPFS was 0.46 (95% CI, 0.32 to 0.66). The median rPFS was not estimable (95% CI, 41 to NE) in the niraparib plus AAP arm vs 26 months (95% CI, 18 to 28) in the placebo plus AAP arm.

Data from 373 patients with non-BRCA2-mutated mCSPC showed a HR for rPFS of 0.88 (95% CI, 0.63 to 1.24). According to the FDA, this indicated “that the overall improvement was primarily attributed to the results seen in patients with BRCA2m.”

At the first interim analysis for overall survival (OS), there were 91 deaths in the BRCA2m population, of which 36 (22%) were in the niraparib plus AAP arm and 55 (34%) were in the placebo plus AAP arm.

In the overall trial population, grade 3 or 4 adverse events (AEs) occurred in 75.2% of patients in the niraparib plus AAP arm vs 58.9% of patients in the placebo plus AAP arm. The most frequent grade 3 or 4 AEs were anemia (29.1% vs 4.6%) and hypertension (26.5% vs 18.4%). Serious AEs were reported in 39.2% of patients in the treatment arm vs 27.6% of patients in the comparator arm. Treatment-emergent AEs leading to death occurred in 14 patients in the niraparib plus AAP group vs 7 patients in the placebo plus AAP group.

According to the FDA, "The recommended dose is 200 mg niraparib and 1,000 mg abiraterone acetate orally once daily in combination with 5 mg prednisone once daily until disease progression or unacceptable toxicity. Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy."

REFERENCES

1. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. News release. US Food & Drug Administration. 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. 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. Nat Med. Published online October 7, 2025. doi:10.1038/s41591-025-03961-8