Niraparib and Abiraterone Acetate Plus Prednisone Approved for BRCA2-Mutated Metastatic CSPC
Expert Perspectives · Keira Smith · 2025-12-22
The FDA has approved niraparib and abiraterone acetate plus prednisone (Akeega®, Janssen Biotech, Inc.) for adults with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC), as determined by an FDA-approved test.
Why This Approval Matters
“Deleterious germline or somatic alterations in homologous recombinant repair (HRR) genes are associated with poor prognosis and occur in up to 25% of patients with CSPC, with BRCA2 being the most commonly altered,” wrote Gerhardt Attard, MD, PhD, Professor of Medical Oncology at University College London, and colleagues, in their publication of the AMPLITUDE trial (NCT04497844), on which the approval was based. “Niraparib is a highly selective, potent PARP inhibitor. We aimed to evaluate whether the combination of a PARP inhibition and an androgen receptor pathway inhibitor at response to first-line androgen deprivation would be effective.”
Breaking Down AMPLITUDE
Efficacy was studied in AMPLITUDE, a randomized, double-blind phase 3 trial that enrolled 696 patients with HRR gene–mutated metastatic CSPC. Patients were randomized to receive niraparib and AAP, or placebo and AAP. All patients also continued to receive androgen deprivation therapy.
The primary end point was investigator-assessed radiographic progression-free survival (rPFS), with overall survival (OS) as a secondary end point.
In the overall population of patients with HRR gene–mutated mCSPC, niraparib plus AAP demonstrated a statistically significant improvement in rPFS compared with placebo.
In an exploratory analysis of 323 patients with BRCA2 mutations, the hazard ratio for rPFS was 0.46, with median rPFS not estimable for niraparib plus AAP versus 26 months for placebo plus AAP. In an exploratory analysis of 373 patients without BRCA2 mutations, the hazard ratio for rPFS was 0.88, suggesting that the overall improvement was attributed primarily to the results observed in the BRCA2 mutation population.
At the first interim OS analysis, there were 91 deaths in the BRCA2 mutation group, including 36 (22%) in the niraparib plus AAP arm and 55 (34%) in the placebo plus AAP arm.
Managing Adverse Events
The prescribing information includes warnings and precautions for myelodysplastic syndromes/acute myeloid leukemia, myelosuppression, hypokalemia, fluid retention, cardiovascular adverse events, hepatotoxicity, adrenocortical insufficiency, hypoglycemia, increased fractures and mortality in combination with radium Ra 223 dichloride, posterior reversible encephalopathy syndrome, and embryo-fetal toxicity.
Dosing and Administration
The recommended dose is niraparib 200 mg 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.
Conclusion
“Combining niraparib with AAP significantly improved rPFS in patients with mCSPC harboring BRCA1/BRCA2 or other HRR gene alterations, suggesting clinical benefit with this combination for these patients,” concluded Dr. Attard and colleagues.
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