On August 11, 2023, the fixed-dose combination of the PARP inhibitor niraparib and the CYP17 inhibitor abiraterone acetate plus prednisone was approved for patients with deleterious or suspected deleterious BRCA-mutated castration-resistant prostate cancer, as determined by a U.S. Food and Drug Administration–approved test.¹

Supporting Efficacy Data

Approval was based on findings in a subgroup of 225 patients with BRCA mutations in a cohort of the double-blind MAGNITUDE trial (ClinicalTrials.gov identifier NCT03748641). Patients were randomly assigned to niraparib at 200 mg, abiraterone at 1,000 mg once daily, plus prednisone at 10 mg daily (n = 113) or placebo, abiraterone, and prednisone (n = 112) until unacceptable toxicity or disease progression.

Median radiographic progression-free survival was 16.6 months (95% confidence interval [CI] = 13.9 months to not estimable) in the niraparib/abiraterone group vs 10.9 months (95% CI = 8.3–13.8 months) in the control group (hazard ratio [HR] = 0.53, 95% CI = 0.36–0.79, P = .0014). In an exploratory analysis, median overall survival was 30.4 vs 28.6 months (HR = 0.79, 95% CI = 0.55–1.12).

How It Is Used

The fixed-dose combination includes niraparib at 200 mg and abiraterone at 1,000 mg once daily, which is used in combination with prednisone at 10 mg until disease progression or unacceptable toxicity. Patients should receive a concurrent gonadotropin-releasing hormone analog or should have received bilateral orchiectomy.

The labeling provides instructions on dosage modification for adverse reactions including myelosuppression and hepatotoxicity. Concomitant use should be avoided for strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin) and CYP2D6 substrates (metoprolol, duloxetine, oxycodone), for which minimal changes in concentration may lead to serious toxicities. Use of niraparib/abiraterone should be avoided in patients with moderate or severe hepatic impairment.

Safety Profile

Among patients in MAGNITUDE with BRCA-mutated disease, the most common adverse events of any grade in the niraparib/abiraterone group were musculoskeletal pain (44% vs 42% in control group), fatigue (43% vs 30%), constipation (34% vs 20%), hypertension (33% vs 27%), and nausea (33% vs 21%). The most common grade 3 or 4 adverse events included hypertension (14% vs 17%), COVID-19 (7% vs 4%), and fatigue (5% vs 4%). The most common grade 3 or 4 laboratory abnormalities were decreased hemoglobin (26%), lymphocytes (22%), platelets (8%), and neutrophils (6%).

Serious adverse events occurred in 41% of patients in the niraparib/abiraterone group, most commonly COVID-19 (7%), anemia (4.4%), pneumonia (3.5%), and hemorrhage (3.5%). Adverse events led to discontinuation of treatment in 15% of patients, most commonly COVID-19 (4.4%), anemia (2.7%), asthenia (2.7%), and vomiting (2.7%). Fatal adverse events occurred in 9% of patients, including COVID-19 (5%), cardiopulmonary arrest (1%), dyspnea (1%), pneumonia (1%), and septic shock (1%).

Fixed-dose niraparib/abiraterone has warnings/precautions for myelodysplastic syndrome/acute myeloid leukemia; myelosuppression; hypokalemia, fluid retention, and cardiovascular adverse reactions; hepatotoxicity; adrenocortical insufficiency; hypoglycemia; increased fractures and mortality in combination with radium Ra-223 dichloride; posterior reversible encephalopathy syndrome; and embryofetal toxicity. 

REFERENCE

1. Akeega (niraparib and abiraterone acetate) tablets, for oral use, prescribing information, Janssen Pharmaceutical Companies, August 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216793s000lbl.pdf. Accessed September 5, 2023.