FDA Approves Niraparib Regimen in BRCA2+ Metastatic CSPC

Data from the phase 3 AMPLITUDE trial support the approval of niraparib plus abiraterone acetate and prednisone for this metastatic CSPC population.

The FDA has approved niraparib and abiraterone acetate (Akeega) in combination with prednisone as a treatment for adult patients with suspected or delterious BRCA2-mutated metastatic castration-sensitive prostate cancer (CSPC), according to a release from the agency.1

Supporting data for the approval came from the phase 3 AMPLITUDE trial (NCT04497844), in which investigators assessed 696 patients with homologous recombination repair (HRR)–mutated metastatic CSPC.2 Investigators randomly assigned patients 1:1 to receive niraparib or matched placebo in combination with abiraterone acetate and prednisone; all were assigned to receive androgen deprivation therapy.

Topline data showed that among 323 patients with BRCA2-mutated disease, the median radiographic progression-free survival (rPFS) was not estimable (NE; 95% CI, 41 months-NE) in the niraparib arm vs 26 months (95% CI, 18-28) in the placebo arm (HR, 0.46; 95% CI, 32-0.66). Additionally, among 373 patients in an exploratory analysis without BRCA2 mutations, the hazard ratio for rPFS was 0.88 (95% CI, 0.63-1.24), suggesting that the rPFS improvement with the niraparib regimen was mostly attributable to the population with BRCA2 mutations.

The first interim analysis for overall survival (OS) showed that 91 deaths occurred in the BRCA2 mutation population, which included 36 in the niraparib arm as well as 55 in the placebo arm.

Prescribing information for the regimen includes warnings for myelodysplastic syndrome or acute myeloid leukemia, myelosuppression, fluid retention, hepatoxicity, hypogylcemia, and increased fractures and mortality in combination with adium Ra 223 dichloride, among others.

The agency approved niraparib at a dose of 200 mg and abiraterone acetate at 1000 mg orally once a day plus prednisone at 5 mg once daily. Patients are recommended to continue treatment until progressive disease or unacceptable toxicity while concurrently receiving a gonadotropin-releasing hormone analog or with bilateral orchiectomy.

References

1. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. News release. FDA. December 12, 2025. Accessed December 12, 2025. https://tinyurl.com/rcxaj98
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. Nature. 2025. doi:10.1038/s41591-025-03961-8