Niraparib (PARP inhibitor) is proven to be tolerable and displayed antitumor activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (DRDs), especially in those having BRCA alterations.

• This multicenter, open-label, single-arm, phase 2 study included 289 eligible participants, to report the antitumor activity as well as safety of niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous therapy with an androgen signaling inhibitor and a taxane.

• Enrolled patients were administered niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination.

• An objective response rate of 34·2% (95% CI 23·7–46·0) was obtained in the measurable BRCA cohort (n=76), with a median follow-up of 10·0 months (IQR 6·6–13·3), at final analysis.

• Nausea (169 [58%] of 289), anemia (156 [54%]), and vomiting (111 [38%]) were identified to be the most common treatment-emergent adverse events of any grade; the most common grade 3 or worse events were hematological (anemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]).

• At least one serious treatment-emergent adverse event occurred in 46%, the most common were also hematological.

• Two adverse events with fatal result (one case with urosepsis in the BRCA cohort and one case with sepsis in the non-BRCA cohort) were deemed likely associated with niraparib use.