Niraparib and Abiraterone Combination Receives FDA Approval for Prostate Cancer

BRCA mutation -positive metastatic castration-resistant prostate cancer (mCRPC) in adults was the indication for first-line treatment with niraparib and abiraterone acetate (Akeega, Janssen Pharmaceuticals), approved by the FDA (US Food and Drug Administration) on August 11, 2023.

Alongside lung cancer, prostate cancer is one of the two most common cancers in men. Patients with BRCA gene mutations, who represent 10-15% of those developing metastatic castration-resistant prostate cancer, may face particularly aggressive disease and poor outcomes. Developing new treatment options is therefore crucial. The details of a new combination treatment approved by the FDA are presented below.

FDA Approval Based on the MAGNITUDE Study

The FDA approval is based on the findings of the phase 3 MAGNITUDE clinical trial.

In Cohort 1 of MAGNITUDE, a randomized, double-blind, placebo-controlled trial was conducted in patients with homologous recombination repair (HRR) gene mutations: 423 patients with mCRPC were included.

Patients were randomized to two arms in a 1:1 ratio:

• Experimental Arm: niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg daily, and
• Control Arm: placebo and abiraterone acetate plus prednisone daily.

Patients were required to have undergone orchiectomy or to be receiving gonadotropin-releasing hormone (GnRH) analogs.

Patient Selection

Patients with mCRPC were eligible if they had not previously received systemic therapy in the mCRPC setting. They could have received docetaxel or androgen receptor (AR)-targeted treatments at earlier disease stages. Randomization was stratified by prior docetaxel, prior AR-targeted therapy, prior abiraterone acetate plus prednisone, and BRCA status.

Second Interim Analysis Results From MAGNITUDE

• Patients With BRCA Mutations: Of the 423 patients, 212 had prespecified BRCA gene mutations (BRCAm). No benefit was observed in patients with mCRPC without HRR gene mutations (Cohort 2 of MAGNITUDE).
• Niraparib + abirateton + prednisone (experimental arm) reduced the risk of radiographic progression by 45% in BRCA1/2-positive mCRPC (median follow-up 24.8 months).
• Main Efficacy Measure: The study's primary endpoint was radiographic progression-free survival (rPFS) , while overall survival (OS) was a secondary endpoint.
• Statistical Improvement: In patients with BRCA gene mutations, median radiographic progression-free survival (rPFS) was 19.5 months in the experimental arm versus 10.9 months in the control arm (hazard ratio [HR] = 0.55 [95% confidence interval [CI] 0.39-0.78).
• OS Analysis in BRCAm Patients: Median survival was 30.4 versus 28.6 months (HR 0.79; 95% CI: 0.55, 1.12). This result also favored the experimental arm.
• rPFS in the Overall Patient Group: In the subgroup of 198 patients (47%) with non-BRCA HRR mutations, the rPFS hazard ratio was 0.99 (95% CI: 0.67, 1.44) and the OS hazard ratio was 1.13 (95% CI: 0.77, 1.64), indicating that the improvement was mainly in BRCAm patients.

Side Effects

The most common side effects and laboratory abnormalities (in 20% or more) among patients with mCRPC treated with niraparib and abiraterone acetate plus prednisone in Cohort 1 of MAGNITUDE were:

• Decreased hemoglobin
• Decreased lymphocytes
• Decreased white blood cells
• Musculoskeletal pain
• Fatigue
• Decreased platelets
• Increased alkaline phosphatase
• Constipation
• Hypertension
• Nausea
• Decreased neutrophils
• Increased creatinine
• Increased potassium
• Decreased potassium
• Increased AST

Need for Blood Transfusions

27% of patients required a blood transfusion, and 11% of these required more than one transfusion.

Dosage and Administration

The recommended dose is 200 mg niraparib and 1000 mg abiraterone combined with 10 mg prednisone once daily until disease progression or unacceptable side effects.

Conclusion: Steps Toward the Future

This new approval represents an important step in prostate cancer treatment. Particularly for patients with BRCA gene mutations, the combination may slow disease progression and extend survival. In addition, this treatment approach, when considered alongside earlier major developments such as FDA approval of abiraterone, a corticosteroid and olaparib in BRCA-mutant prostate cancer and FDA approval of talazoparib and enzalutamide in advanced prostate cancer with HRR gene mutations , is seen as part of innovative approaches to prostate cancer treatment.

These developments open new horizons in prostate cancer treatment and offer patients more effective options. Hopefully, these and similar studies will contribute to more effective, personalized ways of treating cancer.

Manage preferences to view external content