Abstract A098: Whole blood assay for rapid detection of AR-v7 in metastatic castration-resistant prostate cancer: No correlation with response to androgen-axis targeting agents

Abstract

Abstract Background: The expression of AR-v7 in circulating tumor cells (CTCs) of mCRPC patients potentially confers treatment resistance to AR-axis targeting agents, though recent data from the ARMOR3-SV study as well as other publications challenge this hypothesis. Due to the potential barriers of developing a reliable CTC platform, our aim was to develop a rapid assay for AR-v7 detection in patient whole blood samples. Method: We created and optimized a whole blood quantitative real-time polymerase chain reaction assay to correlate outcomes of patients on AR-axis targeting agents with expression of AR-v7. The expression of AR-v7 mRNA in whole blood from 47 patients with mCRPC was obtained prior to commencing therapy. Each sample was run in triplicate; positivity was defined as at least two replicates reaching cycle threshold within a standard deviation between cycles of ≤ 0.25. Gene expression was correlated with PSA response rate using Fisher’s exact test. Results: In our cohort, 10 of 47 patients (21%) were AR-v7+. Of patients commencing abiraterone or enzalutamide (37/47 patients, 79%), we observed similar response rates in the AR-v7+ (4/7) patients, compared to the AR-v7 (20/30) patients (57% vs. 66%, P=0.63; Fisher’s exact test). In two patients, early onset of acquired resistance was associated with conversion from AR-v7 to AR-v7+. AR-v7 was not detected in any of the 13 normal male controls. Conclusion: We developed a specific assay for AR-v7 detection in whole blood from mCRPC patients. Similar PSA response rates were seen in AR-v7+ and AR-v7 patients, inconsistent with literature characterizing AR-v7 as a predictive biomarker, but in support of ARMOR3-SV data demonstrating moderate response rates to an AR-axis targeting agent in AR-v7+ patients. Future directions will include cohort expansion, interrogation of other AR variants, and examination of other clinically meaningful endpoints. Citation Format: Sarah To, Edmond Kwan, Heidi Fettke, Maria Docanto, Nicole Ng, Andrew Mant, Phillip Parente, Carmel Pezaro, Lisa Horvath, Lisa Graham, Tilman Todenhofer, Arun Azad. Whole blood assay for rapid detection of AR-v7 in metastatic castration-resistant prostate cancer: No correlation with response to androgen-axis targeting agents [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A098.