Multinational phase 3 trial of niraparib plus abiraterone-prednisone for HRR-deficient metastatic castration-sensitive prostate cancer

The multinational phase 3 AMPLITUDE trial tested whether PARP inhbition within 6 months of starting androgen deprivation therapy for metastatic castration-sensitive prostate cancer (mCSPC) harboring HRR gene alterations would improve radiographic progression-free survival (rPFS). Patients were randomized 1:1 to niraparib plus abiraterone acetate plus prednisone (AAP) or placebo plus AAP. The primary endpoint was met, with significant improvements in rPFS observed first in the BRCA subgroup and then in the ITT population. Overall survival data were not yet mature but favor niraparib (HR 0.79; 95% CI 0.59-1.04). Incidence or grade 3 or 4 adverse events was 75% in the niraparib group and 59% in the placebo group. There were 14 treatment-emergent adverse events leading to death in the niraparib group and 7 in the placebo group. The authors conclude that adding niraparib to AAP was associated with improved rPFS in patients with mCSPC harboring HRR gene alterations.