Ar-V7 And Efficacy Of Abiraterone (Abi) And Enzalutamide (Enza) In Castration-Resistant Prostate Cancer (Crpc): Expanded Analysis Of The Johns Hopkins Cohort.

5012 Background: We previously reported an association between ARV7 detection and poor outcomes with Abi/Enza in 62 CRPC pts (NEJM 2014). Here, we expand our analysis to 202 pts, and also report the prognostic significance of CTC detection in addition to ARV7 detection. Methods: We prospectively enrolled CRPC pts starting Abi or Enza, and examined the prognostic value of CTC detection (+ vs -) and ARV7 detection (+ vs -) using a CTC-based ARV7 mRNA assay. We examined ≥50% PSA responses, PSA progression free survival (PSA-PFS), clinical/radiologic PFS (PFS), and overall survival (OS). We constructed multivariable (MVA) models adjusting for PSA, Gleason sum, number of prior hormone therapies, prior Abi/Enza use, prior taxane use, presence of visceral mets, and ECOG score. We also separately examined the 1st-line (Abi/Enza-naïve) and 2nd-line (post-Abi or Enza) novel hormonal therapy (NHT) settings. Results: 202 pts were enrolled (median f/u 12.9 mo, range 1.3–35.8 mo). CTC+/ARV7+ pts were more likely to have Gleason ≥8 (p= .05), M1 disease at diagnosis (p= .01), higher PSA (p< .01), prior Abi/Enza use (p= .03), prior taxane use (p= .02), and ECOG ≥1 (p= .01). Outcomes for the overall cohort, and separately for the 1st-line and 2nd-line NHT cohorts, are shown in the Table. All correlations remained significant in MVA models. Conclusions: The negative prognostic impact of ARV7 in pts receiving Abi/Enza is confirmed in this expanded analysis, and applies to both the 1st-line and 2nd-line NHT settings. This study is the first to suggest that our CTC-based ARV7 assay should be interpreted using 3 separate prognostic categories (CTC–, CTC+/ARV7-, CTC+/ARV7+). N (%) Overall (N = 202) 1st-Line NHT (N = 124) 2nd-Line NHT (N = 78) CTC n = 53 (26.2%) CTC+/ ARV7 n = 113 (56.0%) CTC+/ ARV7+ n = 36 (17.8%) P CTC n = 36 (29.0%) CTC+/ ARV7 n = 73 (58.9%) CTC+/ ARV7+ n = 15 (12.1%) P CTC n = 17 (21.8%) CTC+/ ARV7 n = 40 (51.3%) CTC+/ ARV7+ n = 21 (26.9%) P PSA response 75% 52% 14% < .001 86% 66% 27% < .001 53% 28% 5% .003 PSA-PFS (mo) 11.3 6.2 2.1 < .001 12.7 7.3 2.9 < .001 6.4 4.4 1.1 < .001 PFS (mo) 13.9 7.7 3.1 < .001 21.6 10.1 4.1 < .001 6.2 5.3 2.8 < .001 OS (mo) 28.7 29.5 11.2 < .001 29.7 30.7 21.5 .003 18.8 13.0 8.5 < .001