FDA Greenlights Niraparib/Abiraterone Acetate With Prednisone in mHSPC

The FDA has greenlit niraparib and abiraterone acetate (AAP; Akeega) with prednisone for the treatment of adults with deleterious or suspected deleterious BRCA2-mutated metastatic hormone-sensitive prostate cancer (mHSPC) identified by an FDA-approved test, based on results from the phase 3 AMPLITUDE trial (NCT04497844).¹

In results from an exploratory analysis of 323 patients enrolled in the trial with BRCA2-mutated mHSPC, niraparib/AAP lowered the risk of death or radiographic progression by 54% vs placebo/AAP (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66).

Median radiographic progression-free survival (rPFS) for patients receiving the combination therapy was not estimable (NE; 95% CI, 41 months-NE) vs 26 months (95% CI, 18-28) for those receiving a placebo/AAP.

An exploratory analysis of patients without BRCA2 mutations demonstrated an HR of 0.88 (95% CI, 0.63-1.24), revealing results were largely attributable to BRCA2 mutational status.

At the first interim analysis for overall survival (OS), 91 deaths occurred in patients harboring BRCA2 deletions, 36 of whom (22%) were on the niraparib/AAP arm and 55 of whom (34%) were on the placebo/AAP arm.

Recommended Dosing for Niraparib/AAP in mHSPC

The recommended dose of this combination is 200 mg of niraparib and 1000 mg of abiraterone acetate taken once daily orally along with 5 mg of prednisone daily. The FDA noted in its announcement of the therapy’s approval that patients should also receive a gonadotropin-releasing hormone (GnRH) analog along with treatment or have already received a bilateral orchiectomy.

Quality-of-Life Fluctuations With Niraparib/Abiraterone Acetate in mHSPC

Data from AMPLITUDE on niraparib/AAP’s impact on health-related quality of life (HR-QOL) via patient-reported outcomes (PROs) were shared at the 2025 ESMO Congress in October.²

With 696 patients randomly assigned 1:1 to either the niraparib and placebo arms, at least 94.3% of patients completed an online questionnaire, which was given to patients at screening, during cycles 1 to 25, and then every 4 months up to the end of treatment.

FACT-G scores were not significantly different in general; however, at cycles 2 and 4, patients in the niraparib/AAP arm reported decreased FACT-G scores where scores for patients in the placebo/AAP arm increased.

Lead study author Dana Rathkopf, MD, a genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, explained during her presentation of the data that this fluctuation was expected and returned to baseline after this period.

“You can see that there was an initial reduction in the HR-QOL score in the niraparib arm, which may have been explained by the onset of the most frequently observed adverse events, which included hypertension and anemia, which were subsequently well-managed,” said Rathkopf. “The score returned to baseline from cycles 5 and onward.”

Rathkopf also noted that the niraparib arm’s FACT-G scores declined toward the end of the trial.

“There was a slight separation of the curves toward the end for the niraparib arm,” said Rathkopf. “This may have been because there was a higher number of [patients on] niraparib in the last cycles on study.”

The prescribing information for niraparib/abiraterone acetate includes warnings for secondary malignancies including myelodysplastic syndrome and acute myeloid leukemia, myelosuppression, hypokalemia, fluid retention and cardiovascular adverse reactions, hepatoxicity, adrenocortical insufficiency, hypoglycemia, increased fractures and mortality in combination with radium dichloride (Xofigo), posterior reversible encephalopathy syndrome, and embryo-fetal toxicity.

AMPLITUDE Trial at ASCO

Results from the AMPLITUDE trial were presented at the 2025 ASCO Annual Meeting in June, where lead investigator Gerhardt Attard, MD, PhD, Cancer Institute, University College London, offered commentary on the combination’s prospect in BRCA2-mutated mHSPC.³

“This was a really exciting result,” said Attard. “This is the first study to show efficacy for PARP inhibition and androgen receptor inhibition in CSPC, the benefit [of which] might be greatest in patients with BRCA mutations.”

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. Rathkopf D, Agarwal N, Graff JN, et al. Patient (pt) reported outcomes (PROs) from AMPLITUDE, a randomized placebo-controlled phase III trial of niraparib (NIRA) and abiraterone acetate (AA) plus prednisone (P) in metastatic hormone-sensitive prostate cancer (mHSPC) with homologous recombination repair mutations (HRRm). Presented at: European Society of Medical Oncology 2025 Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA91.
3. 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