FDA Approval Summary: Niraparib plus Abiraterone Acetate Fixed-Dose Combination for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer.

On August 11, 2023, the FDA approved the fixed-dose combination of niraparib and abiraterone acetate (AA), with prednisone (AAP), for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer, as determined by an FDA-approved test. Substantial evidence of effectiveness was demonstrated by cohort 1 of MAGNITUDE (NCT03748641), a multi-cohort study. Cohort 1 was a double-blind trial that randomly assigned 423 patients with metastatic castration-resistant prostate cancer and homologous recombination repair mutations to receive niraparib 200 mg daily plus AA 1,000 mg daily and prednisone versus placebo plus AAP. The presence of BRCAm was a stratification factor. There was a statistically significant improvement in the primary endpoint of radiographic progression-free survival (rPFS) by blinded independent central review in the BRCAm subpopulation: the median rPFS was 16.6 months [95% confidence interval (CI), 13.9-not estimable] in the niraparib + AAP arm and 10.9 months (95% CI, 8.3-13.8) in the placebo + AAP arm (HR, 0.53; 95% CI, 0.36-0.79; P = 0.0014). There was also a statistically significant improvement in rPFS in the all-homologous recombination repair mutation population (intention-to-treat population); however, exploratory analyses conducted by the FDA indicated that this improvement was primarily attributed to the subgroup of patients with BRCAm, which supported limiting the indication to that population. Adding niraparib to AAP resulted in increased toxicity, including anemia requiring transfusion in 27% of patients. This article summarizes the data and the FDA's thought process supporting the traditional approval of niraparib plus AA fixed-dose combination.