The detection of AR-V7 predicts insensitivity to either medication, but identifies only a portion of non-responders. The authors previously identified 15 CTC subtypes based on unique phenotypic features in mCRPC patients, each with distinctive biology and different degree of likelihood of predicting resistance to either drug. The objective of this study was to assess the relationship between individual CTC subtypes and sensitivity to abiraterone versus enzalutamide.
For this study, 107 pre-treatment blood samples from mCRPC patients starting abiraterone (n = 47) or enzalutamide (n = 60) as a 1st or 2nd line of treatment were analyzed for CTCs. Treatment outcomes were assessed by serial PSA changes and landmarked percent time of therapy progression on imaging, and overall survival (OS) following either abiraterone or enzalutamide. Cell type prevalence was also analyzed as related to clinical outcomes and subsets of the CTC subtypes were subject to single cell next generation sequencing to assess genomic drivers common to each subtype.
CTCs were identified in 94% of samples, including cell Type K found in 25% of patients. This cell type was associated with significantly inferior outcomes for enzalutamide for all measures, whereas there was no association with outcomes for K+ or K- patients treated with abiraterone. For patients treated with enzalumatide who were K+ compared to K-, there was poorer outcomes for patients with >50% PSA decline, percent of patients >6 months on treatment, radiographic PFS and 1-year OS outcomes. The cellular features of cell Type K include a large nucleus, high nuclear entropy, and high nuclear/cytoplasmic AR terminal ratio. Furthermore, this cell type had a unique genomic profile with high levels of cell cycle and DNA repair alterations when compared to other CTC subtypes.
In conclusion, the authors stated that the presence of specific CTC subtypes in pre-treatment samples was associated with outcomes on abiraterone or enzalutamide. A CTC subtype (cell Type K) is present in 25% of patients with a unique phenotypic and genotypic profile, helping to identify patients with poor outcomes on enzalutamide, but not abiraterone. This has the potential to support cell Type K as a possible biomarker for stratifying patients to abiraterone versus enzalutamide. Further biologic examination of K cells and ongoing clinical validation of the CTC subtype is planned.
Presented By: Howard I. Scher, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Co-Authors: Adam Jendrisak, Nicole A. Schreiber, Brigit McLaughlin, Ryon P Graf, Angel Rodriguez, Martin Fleisher, Jerry Lee, James Kelvin, Yipeng Wang, Mark Andrew Landers, Ryan Vance Dittamore
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA