ASCO 2017: Identification of a CTC-based gene expression signature predicting resistance to abiraterone and enzalutamide in mCRPC

Chicago, IL ( Dr. Todd Morgan and collaborators presented their work at the ASCO 2017 prostate cancer poster session assessing a circulating tumor cell (CTC)-based gene expression signature predicting resistance to abiraterone and enzalutamide in mCRPC patients. CTC-based detection of AR-V7 has been shown to predict response to 2nd generation AR therapies, however the rarity of AR-V7 is indicative of needing to identify additional biomarkers in this setting to predict response. The objective of this study was to utilize a multiplex gene expression platform for assessing CTCs in order to determine other predictive biomarkers of response.

For this study, 5mL of whole blood was obtained from 37 patients with mCRPC starting enzalutamide (n=16) or abiraterone (n=21). Following cell lysis, mRNA was extracted followed by multiplex qRT-PCR for 92 prostate cancer-related genes. Genes were identified associated with PSA and radioclinical progression free survival (PFS) using Cox regression analysis, and multi-gene models were tested using ROC analysis. Fifty-four percent of patients had detectable CTCs, with no difference in detectability when assessing enzalutamide or abiraterone. Seven genes (AR, AR-V7, ANXA2, SOX2, PSCA, PSA, WNT5B) were associated with both PSA PFS and radioclinical PFS in the Cox analyses over a median follow-up of 11.4 months (IQR 3.9-19.4). Combing the seven genes into a single model gave AUC values of 0.88 for PSA PFS and 0.89 for radioclinical PFS. By comparison, the AR-V7-only model resulted in AUC values of 0.65 and 0.66, respectively.

In conclusion, this is an elegant novel gene assay that identified prostate cancer-related genes that can be determined from CTCs and appear to predict short time to progression in men with mCRPC being treated with 2nd generation hormonal therapies. As the authors mention, this does need prospective validation, but the feasibility demonstrated in this study will guide larger prospective trials moving forward.

Presented By: Todd M. Morgan, MD, University of Michigan, Ann Arbor, MI, USA

Co-Author(s): Jae-Seung Chung, Yugang Wang, James Henderson, Udit Singhal, Yuanyuan Qiao, Alexander Zaslavsky, Daniel H Hovelson, Ajjai Shivaram Alva, Felix Yi-Chung Feng, Ganesh S. Palapattu, Russell S. Taichman, Arul M. Chinnaiyan, Scott A. Tomlins

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada 
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA