Abstract LB-045: Cogency of AR-V7 unexpected responders determined by using distinct detection technologies

Abstract

Abstract Background: The validity of AR-V7 in CTC’s as a predictive marker for non-response to next generation ADT (abiraterone or enzalutamide) has recently been questioned. Specifically, a subset of AR-V7 positive patients showed responses to abiraterone or enzalutamide and assay performance differences could contribute to these unexpected findings. [[Unsupported Character - Codename ­]]To our knowledge a direct performance comparison has not been performed. Here we present comparative head to head analysis of different AR-V7 detection technologies with respect to specificity, accuracy and clinical sensitivity. Methods: We performed comparison of two different AR-V7 detection technologies using either SYBR Green or TaqMan chemistry. Both assays were tested on identical in vitro samples consisting of genitourinary cancer cell lines as well as dilution series of AR-V7 positive cDNA samples. Finally, clinical samples with previously determined CTC and AR-V7 status using TaqMan chemistry were re-analyzed using SYBR Green chemistry. Results: Both assays performed identical in detection of AR-V7 in different genitourinary cancer cell lines. Additionally, by performing dilution series analyses we observed the same diagnostic threshold of both assays. When re-analysis of clinical samples was performed, both assays performed undistinguishable in determination of the AR-V7 status of mCRPC patients, including 3 patients exhibiting unexpected response to NHT despite AR-V7 positive CTCs. Finally, loss of AR-V7 positive CTCs in serial CTC analysis of one patient during abiraterone treatment was observed using both detection assays. Conclusion: By demonstrating nearly identical performance metrics, we excluded assay design differences as an underlying reason for the unexpected responses in a subset of AR-V7 patients. Interestingly, for the first time, we detected an AR-V7 positive mCRPC patient displaying a loss of AR-V7 positive CTCs during NHT therapy. These findings underscore that - irrespective of the method used - AR-V7 positive patients should not systematically be precluded from an otherwise safe treatment attempt. Citation Format: Christof Bernemann, Verena Humberg, Martin Bögemann, Andres J. Schrader, Julie Steinestel, Jochen K. Lennerz. Cogency of AR-V7 unexpected responders determined by using distinct detection technologies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-045. doi:10.1158/1538-7445.AM2017-LB-045