Phenotypic And Genomic Characterization Of Ctcs As A Biomarker For Prediction Of Veliparib Therapy Benefit In Mcrpc.

5012Background: Response to PARPi in mCRPC patients (pts) particularly those with DNA damage response mutations (DDRm) was observed in the TOPARP trials (utilizing Olaparib) which enrolled heavily pre-treated, high CTC pts. However, the NCI 9012 study, randomizing 1st line mCRPC pts to Abiraterone (A) or A + Veliparib (V), did not demonstrate an advantage for V in any pre-specified subgroup, with DDRm pts having better outcomes on both arms. Here we explore the use of CTCs to ascertain phenotypic Genomic Instability (pGI) as a proposed selection biomarker for PARPi. Methods: 212 blood samples from 84 pts (n = 39 A u0026 n = 42 A+V, 3 uneval) prior to and during therapy were processed utilizing the Epic Sciences CTC platform. 32 pts had a concomitant fresh biopsy sequenced by MI-ONCOSEQ. CTC pGI was determined using previously described algorithms (Scher et al. ASCO 2016) which predicts genomic instability with morphological features and protein expression. A subset of CTCs (n = 466) underwent single cell sequ...