Androgen receptor (AR) amplification in patients with metastatic castration-resistant prostate cancer (mCRPC) refractory to therapy with abiraterone acetate or enzalutamide: Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).

Abstract

5020 Background: The mechanisms of resistance to androgen signaling inhibitors such as Abiraterone (Abi) or Enzalutamide (Enz) are poorly understood. AR amplification (AR+) has been observed in Abi/Enz naive mCRPC patients (pts), but its role in Abi/Enz resistant pts is not known. Progressive mCRPC has historically been challenging to biopsy and characterize on a molecular basis because of its bone tropism. As part of the WCDT project which aims to identify genetic pathways underlying primary and acquired resistance to Abi and Enz, AR+ was assessed in mCRPC biopsies. Methods: Following central radiologic review, eligible mCRPC pts underwent biopsy at one of 5 WCDT clinical sites, using a uniform biopsy protocol. Tissue was both frozen, and formalin fixed/paraffin embedded (FFPE). FFPE tissue underwent a CLIA-certified assessment of a mutational panel, IHC for PTEN, and fluorescence in situ hybridization (FISH) for AR+. Results: 60 of 300 planned mCRPC pts have undergone a metastasis biopsy. To date, 33 pt...