In the U.S., most mCRPC patients will receive an ARSi (abiraterone, enzalutamide) in 1st line. More than 60% will receive a second, sequential ARSi (A-A) as opposed to ARSi then Taxane (A-T). No randomized studies exist comparing A-A and A-T. Recent real-world cohort risk-adjusted analyses were not able to discern differences in overall survival (OS) between A-A and A-T, despite a wide range of observed outcomes within groups. Using a cross-sectional cohort of standard of care in a tertiary center, we sought to determine if observations were consistent with community, and evaluate if nuclear AR-V7 could have additive effect on OS, specifically post-ARSi failure.
We previously reported utility of nuclear AR-V7 in two cross-sectional cohorts (Scher et al 2016 and Scher et al 2018). Blood was drawn from mCRPC patients prior to new line of therapy, AR-V7 testing by Epic Sciences, and therapy choice by physician without knowledge of AR-V7 status. OS data was updated, and a subset of these combined cohorts were analyzed (n = 148): those who had failed an ARSi, and were about to go onto a second ARSi (n = 73) or taxane (n = 75). A risk score was used to adjust for underlying patient imbalances and therapy choice propensity.
75 of 148 (51%) received A-T and 73 of 148 (49%) received A-A. Adjusting for patient risk, a discernable difference in OS was not detected (HR: 1.16, CI: 0.73 – 1.85, p = 0.52). Incorporating AR-V7, there was a significant interaction between positivity for AR-V7 and OS on taxanes (HR: 0.16, CI: 0.052 – 0.52, p = 0.0020). In risk-matched analysis, there was a significant difference in OS between AR-V7(+) patients on taxanes vs. ARSi (11.6mo vs. 5.5mo, p = 0.0029).
Sequential ARSi use in the U.S. is common. Adjusting for patient risk and physician therapy choice, AR-V7 use after ARSi failure identifies patients who would live longer on taxanes vs. ARSi. Physician intuition alone was not sufficient to achieve predictive effect of AR-V7.
Clinical trial identification
Legal entity responsible for the study
NIH/NCI P50-CA92629 SPORE in Prostate Cancer, NIH/NCI Cancer Center Support Grant P30-CA008748, NIH grant R01-CA207220, Department of Defense Prostate Cancer Research Program (PC121111 and PC131984), Prostate Cancer Foundation Challenge Award, and David H. Koch Fund for Prostate Cancer Research.
H.I. Scher: Consultant: Sanofi, Clovis, Janssen, Pfizer; Grant/research support to MSK: Innocrin, Janssen; Board of directors: Asterias Biotheraputics; Advisory board: WCG Oncology. R.P. Graf: Employee: Epic Sciences, Inc. R. Dittamore: Employee of Epic Sciences. All other authors have declared no conflicts of interest.