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.