1647P - Clinical validity of plasma DNA testing to identify BRCA-mutated (BRCA+) patients in the MAGNITUDE study

Background

Niraparib plus abiraterone acetate with prednisone (NIRA+AAP) is indicated for BRCA+ metastatic castration-resistant prostate cancer (mCRPC) patients (pts), as identified by an approved companion diagnostic tissue test, Foundation One®CDx (F1CDx®). We evaluated the clinical utility of a plasma assay (FoundationOne®Liquid CDx, F1LCDx®) to identify BRCA+ pts in the MAGNITUDE study.

Methods

BRCA status was prospectively evaluated in MAGNITUDE pts utilizing both tissue (F1CDx) and plasma (Resolution Bioscience) clinical trial assays (CTAs). Plasma testing by F1LCDx was performed retrospectively. Concordance of BRCA status by F1LCDx with a) all CTAs and b) tissue (F1CDx) was evaluated. Clinical utility of F1LCDx was explored by comparing radiographic progression-free survival (rPFS) between treatment arms in BRCA+ pts identified by F1LCDx and enrolled by a) CTAs and b) by F1CDx in MAGNITUDE.

Results

In 443 pts with available plasma samples, 396 had evaluable F1LCDx results (89%). In these 396 pts, there was 74% (95% CI: 67%, 79%) positive percent agreement (PPA) and 97% (94%, 99%) negative percent agreement (NPA) between F1LCDx and CTA. Among the samples with valid F1LCDx and F1CDx results, prevalence-adjusted PPV was 73% (59%, 89%) and NPV was 97% (97%, 98%). Clinical efficacy of F1LCDx vs CTAs and F1LCDx vs F1CDx in BRCA+ pts is shown in the table. Table: 1647P

^aNE (not estimable) = Median could not be estimated due to low number of events^bCTA+ (positive by F1CDx tissue and/or RB plasma)^cF1CDx+ (BRCA+ by only F1CDx tissue)

Conclusions

Clinical efficacy of NIRA+AAP was consistent in F1LCDx-identified BRCA pts compared to CTA and tissue identified pts, demonstrating the potential clinical utility of the F1LCDx plasma assay as a non-invasive test.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Janssen Research & Development, LLC.

Funding

Janssen Research & Development, LLC.

Disclosure

G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion, Novartis; Financial Interests, Personal, Royalties: Institute of Cancer Research; Financial Interests, Institutional, Invited Speaker: Artera, Veracyte, Janssen, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Janssen, Astellas, Novartis; Non-Financial Interests, Personal, Principal Investigator: Janssen, Astellas; Non-Financial Interests, Personal, Advisory Role: Janssen, AstraZeneca; Non-Financial Interests, Personal, Project Lead: Artera, Veracyte. U. Singh, Y. Xu, L. Farrington, S. Wang: Financial Interests, Personal, Other, Employee: Janssen Research & Development, LLC; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. K. Bell, K. Urtishak: Financial Interests, Personal, Other, Employee: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. W. Kim, J. Zhang, S. Parsons: Financial Interests, Personal, Other, Employee: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. K.Y. Li, M. Schwenk: Financial Interests, Personal, Other, Employee: Foundation Medicine; Financial Interests, Personal, Other, A wholly owned subsidiary: Roche; Financial Interests, Personal, Other, Equity interest: Roche. W. Li: Financial Interests, Personal, Other, Employee: Foundation Medicine; Financial Interests, Personal, Other, wholly owned subsidiary: Roche; Financial Interests, Personal, Other, equity interest: Roche.