Abstract 4954: Nuclear localized AR-V7 protein as a predictive biomarker for treatment selection in metastatic castration resistant prostate cancer (mCRPC)
Authors: Howard I. Scher, David Lu, Nicole A. Schreiber, Jessica Louw, Ryon P. Graf, Ann Johnson, Adam Jendrisak, Glenn Heller, Richard Bambury, Herbert A. Vargas Alverez, Brigit McLaughlin, Justin Wahl, Stephanie Greene, Martin Fleisher, Ryan Dittamore
Journal: Cancer Research (2016)

Abstract Background: A critical decision in the management of patients (pts) with mCRPC is when to administer an androgen receptor signaling (ARS) directed or a taxane therapy. The detection of AR-V7 mRNA in CTCs has been shown to predict for resistance to ARS,but not to taxane chemotherapy. We evaluated the relationship between AR-V7 protein expression and localization on CTCs to treatment outcomes in a separate, larger cohort as a predictive biomarker for clinical decision making. Methods: 193 prospectively collected blood samples from 161 unique pts with progressive mCRPC about to start an ARS or taxane therapy were evaluated with an Epic Sciences CTC immunoflorescent assay that assesses CTC AR-V7 protein expression and localization in individual cells. Associations between the presence AR-V7(+) CTCs pre-therapy and anti-tumor effects post-therapy included prostate-specific antigen (PSA) changes, radiographic progression free survival (rPFS), time on therapy, and overall survival (OS). Results: 130 pre-ARS inhibitor and 63 pre-taxane samples were assessed of which 191 (99%) were evaluable. AR-V7(+) CTCs were found in 34 (18%) samples including 3% of the 1st, 18% of the 2nd and 31% of the 3rd+ line baseline pre-therapy samples. Patients with AR-V7 positive CTCs in a pre-ARS sample showed no PSA response and had shorter rPFS, time on therapy, and OS than those without AR-V7(+) CTCs. PSA resistance to ARS was also seen in 65 of 112 (58%) of the AR-V7(-) samples. There was no association between PSA response, rPFS, and time on therapy between AR-V7(+) and AR-V7(-) pts treated with taxane therapy. In a multivariate model adjusting for age, type of therapy, line of therapy, and pre-therapy LDH, Hgb, and presence of visceral metastasis, AR-V7(+) pts had a superior OS on taxane therapy relative to ARS (HR: 0.242, CI: 0.103 to 0.569, p = 0.0350). Conclusions: The results validate the expression of the AR-V7 protein in the nucleus of CTCs in men with mCRPC as a treatment specific biomarker that predicts resistance to ARS inhibitor therapy and separately, clinical benefit with taxane therapy over ARS-directed therapy in a clinical practice setting. Continued examination of this biomarker in prospective studies will further determine its clinical utility. Citation Format: Howard I. Scher, David Lu, Nicole A. Schreiber, Jessica Louw, Ryon P. Graf, Ann Johnson, Adam Jendrisak, Glenn Heller, Richard Bambury, Herbert A. Vargas Alverez, Brigit McLaughlin, Justin Wahl, Stephanie Greene, Martin Fleisher, Ryan Dittamore. Nuclear localized AR-V7 protein as a predictive biomarker for treatment selection in metastatic castration resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4954.