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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Monday, August 14, 2023
On August 11, 2023, the U.S. Food and Drug Administration (FDA) approved the fixed-dose combination of niraparib and abiraterone acetate (Akeega), with prednisone, for adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer, as determined by an FDA-approved test.
Efficacy was evaluated in Cohort 1 of MAGNITUDE, a double-blind, placebo-controlled trial enrolling 423 patients with homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer. Patients were randomly assigned (1:1) to receive niraparib at 200 mg and abiraterone acetate at 1,000 mg plus prednisone at 10 mg daily or placebo and abiraterone acetate plus prednisone daily. Patients were required to have a prior orchiectomy or be receiving a gonadotropin-releasing hormone analog. Approximately half of patients had prospectively determined BRCA gene mutations. No benefit was observed in patients without an HRR gene mutation (Cohort 2 of MAGNITUDE), as the criterion for futility was met.
A statistically significant improvement in radiographic progression–free survival with the niraparib combination compared with placebo and abiraterone acetate plus prednisone was observed in patients with BRCA mutations, with a median of 16.6 months vs. 10.9 months (hazard ratio [HR] = 0.53; 95% confidence interval [CI] = 0.36–0.79; P = .0014). An exploratory overall survival analysis in patients with BRCA mutations demonstrated a median of 30.4 vs. 28.6 months (HR = 0.79; 95% CI = 0.55–1.12) favoring the investigational arm. Although a statistically significant improvement in radiographic progression–free survival was seen in the overall Cohort 1 intention-to-treat HRR population (HR = 0.73; 95% CI = 0.56–0.96; P = .0217), in the subgroup of 198 patients (47%) with non-BRCA HRR mutations, the radiographic progression–free survival hazard ratio was 0.99, and the overall survival hazard ratio was 1.13, indicating the improvement in the intention-to-treat HRR gene–mutated population was primarily attributed to the results seen in the subgroup of patients with BRCA mutations.
The most common adverse reactions (≥ 20%) 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, and increased aspartate aminotransferase.
For full prescribing information, visit accessdata.fda.gov.
U.S. Food and Drug Administration
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