Clinical Performance of Tissue- and Plasma-Based Diagnostic Assays in Identifying Homologous Recombination Repair Gene Alterations in Patients with Metastatic Castration-Resistant Prostate Cancer following Treatment with Niraparib with Abiraterone Acetate Plus Prednisone (Niraparib + AAP).

This retrospective study was designed to demonstrate the clinical utility of two diagnostic tests, the FoundationOneCDx (F1CDx) and Exact Sciences Resolution homologous recombination deficiency (HRD; Resolution HRD assay) as clinical trial-enrollment assays to identify patients with metastatic castration-resistant prostate cancer harboring homologous recombination repair (HRR) gene alterations. Tumor tissue and plasma collected from patients with metastatic castration-resistant prostate cancer in the phase 3 MAGNITUDE study were tested using the F1CDx tissue assay and/or the Resolution HRD plasma assay. Patients with HRR alterations were randomized (1:1) to receive niraparib (NIRA) and abiraterone acetate (AA) + prednisone (NIRA + AAP) or placebo and AAP (PBO + AAP; NCT03748641). Efficacy was based on radiographic progression-free survival (primary end point), time tosymptomatic progression, time to cytotoxic chemotherapy, and overall survival as secondary end points (interim analysis 1). Of 423 HRR patients, 291 (68.8%) were HRR positive (HRR+) by F1CDx [BRCA+: 162 (38.2%)], and 38 (8.9%) were HRR negative by F1CDx but HRR+ by Resolution HRD assay. Also, 277 of 423 (65.5%) were HRR+ by Resolution HRD assay [BRCA+: 150 (35.5%)], and 124 (29.3%) were HRR negative by Resolution HRD assay but HRR+ by F1CDx assay. Clinically meaningful benefits for all end points were comparable for BRCA+ and HRR+ patients detected by either tissue or plasma assays. These results demonstrated the clinical utility of both tissue and plasma assays in identifying patients for NIRA + AAP treatment.