FDA Greenlights Niraparib/Abiraterone Acetate With Prednisone in mHSPC

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

An exploratory analysis of 323 patients enrolled in the trial with BRCA2-mutated mCSPC found that niraparib and abiraterone acetate with prednisone (AAP) lowered the risk of death or radiographic progression by 54% vs placebo and AAP (HR, 0.46; 95% CI, 0.32-0.66).

Median radiographic progression-free survival 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 and AAP.

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

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

Recommended Dosing for Niraparib-AAP in mCSPC

The recommended dose of this combination is 200 mg of niraparib and 1000 mg of abiraterone acetate taken once daily orally 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 analog along with treatment or should have already had a bilateral orchiectomy.¹

Quality-of-Life Fluctuations With Niraparib-AAP in mHSPC

Data from the AMPLITUDE trial on niraparib-AAP’s impact on health-related quality of life (HRQOL) via patient-reported outcomes were shared at the 2025 European Society for Medical Oncology Congress in October 2025.²

Of the 696 patients randomly assigned 1:1 to the niraparib-AAP or placebo-AAP arms, at least 94% completed the HRQOL online questionnaire administered at screening during cycles 1 to 25 and then every 4 months through the end of treatment. Functional Assessment of Cancer Therapy–General (FACT-G) scores were not significantly different overall; however, at cycles 2 and 4, patients in the niraparib-AAP arm reported decreased FACT-G scores and patients in the placebo-AAP arm reported increased scores.²

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.²

“You can see that there was an initial reduction in the HRQOL 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,” Rathkopf said.² “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.² “This may have been because there was a higher number of [patients on] niraparib in the last cycles [of the] study.”

The prescribing information for niraparib and AA includes warnings for secondary malignancies (eg, 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 Ra 223 dichloride (Xofigo), posterior reversible encephalopathy syndrome, and embryo-fetal toxicity.³

AMPLITUDE Trial Results at ASCO

Results from the phase 3 AMPLITUDE trial (NCT04497844) were presented at the 2025 American Society of Clinical Oncology Annual Meeting, where lead investigator Gerhardt Attard, MD, PhD, of the Research Department of Oncology at University College London, offered commentary on the prospect of niraparib-AAP in BRCA2-mutated mCSPC.⁴

“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. Updated 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 for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA91.
3. Akeega. Prescribing information. Janssen Biotech, Inc; 2025. Accessed February 5, 2026. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/AKEEGA-pi.pdf
4. Attard G, Agarwal N, Graff J, et al; AMPLITUDE Investigators. 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