Niraparib plus abiraterone and prednisone shows mixed results in HRR-mutated mCRPC

Combination therapy with the PARP inhibitor niraparib and the androgen-receptor inhibitor abiraterone acetate plus prednisone (AAP) has recently shown improvement in radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations, particularly BRCA1/2, in the phase III MAGNITUDE trial. Evidence outside clinical trials remains limited. We retrospectively reviewed the clinical courses of five consecutive patients with HRR-mutated mCRPC treated with niraparib (200 mg once daily) plus abiraterone acetate (1000 mg once daily) and prednisone (5 mg twice daily) at our institution. Baseline characteristics, PSA kinetics (including time to PSA 50% decline), radiological responses, progression-free survival (PFS; defined as a composite clinical, radiological, and biochemical endpoint), overall survival (OS), and safety outcomes were assessed. All patients underwent radiological evaluation every three months, including contrast-enhanced CT of the chest and abdomen and bone scintigraphy. Tumor response was assessed according to RECIST 1.1 criteria for measurable disease. All patients harbored pathogenic HRR gene alterations: somatic and/or germline BRCA1/2 (three BRCA2, two BRCA1), and one patient with concurrent PALB2. Median age at therapy initiation was 70 years (range 60–80). Three patients (Patients 1, 4, 5) achieved significant and sustained PSA declines (≥50%) and prolonged disease control, including elderly and frail individuals. Two patients (Patients 2, 3) exhibited early progression with limited clinical benefit, consistent with aggressive disease course. Median PFS varied widely across the cohort, reflecting heterogeneity of clinical phenotypes. Treatment was generally manageable; dose interruptions or reductions were required in selected cases, with no new safety signals observed. Niraparib–abiraterone demonstrated anti-tumor activity in a subset of HRR-mutated mCRPC patients, including elderly and frail individuals. However, the very small sample size, retrospective design, and absence of standardized rPFS assessment limit generalizability. These findings are primarily hypothesis-generating but align with prospective trial results and underscore the heterogeneity of HRR-mutated mCRPC, highlighting the need for individualized therapeutic strategies.