Nuclear-localized AR-V7 testing of circulating tumor cells (CTCs) has been validated as a predictive biomarker of chemotherapy response and ARSI non-response in 2nd+ line therapy for metastatic castration-resistant prostate cancer (mCRPC). A validation study showed that AR-V7(+) pts have improved OS with taxane chemotherapy, and AR-V7(-) pts have improved OS with ARSi. We assessed the effect of AR-V7 testing on OS when generalized to non-trial clinical settings, as found in third-party US healthcare systems.
The causal effect of treatment and nuclear AR-V7 status on OS was estimated from risk-adjusted hazard rates of the MSK, ICR, LHS validation study. Therapeutic strategies assessed were (1) taxanes only, (2) ARSi only, (3) current US utilization rate of ARSis, and (4) nuclear AR-V7-guided treatment. Quality of life adjustments were extracted from meta-analysis of large cohort studies. We applied US utilization rate of consecutive ARSi administration (abiraterone after enzalutamide, or enzalutamide after abiraterone) and compared to switching with taxane-based chemotherapy (docetaxel after abiraterone, or docetaxel after enzalutamide).
The following table shows OS, adjusted and unadjusted for quality of life, and treatment by strategy. The net effects on OS were robust to variation on the clinical effects, and on systems covariates, e.g., demographic, patient, and payer case-mix.Table: 848P
|2nd line mCRPC therapy strategy||% ARSi||OS (months) QALY (Unadj / Adj.)||Net OS gain (months) QALY (Unadj / Adj)|
|Only use taxanes||0%||19.2 / 12.2||-3.7 /-2.0|
|Only use ARSi’s||100%||25.4 / 15.6||2.5 / 1.4|
|Current use of ARSi (US)||60%||22.9 / 14.2||- REF -|
|AR-V7 guided treatment||77%||27.3 / 16.7||4.4 / 2.5|
Health outcome modeling of the validation data support that current use and access to 2nd ARSi therapy can improve OS of patients over strict use of taxane chemotherapy (+3.7mo OS). 2nd+ line nuclear-localized AR-V7 guided treatment for men with progressive mCRPC provides higher OS than non-guided, almost doubling the gain (+4.4 mo OS) observed with current US utilization rate of ARSi versus taxanes only. Cost effectiveness analyses of the adoption/coverage of nuclear AR-V7 testing in healthcare systems is ongoing.
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 were used to support the design and conduct of the study at Memorial Sloan Kettering Cancer Center. Funds from the London Regional Cancer Program Catalyst Grant and TELUS Ride For Dad/Prostate Cancer Fight Foundation were used to support the study at London Health Sciences Centre. A Medical Council Clinical research Fellowship (AJ) and NHS funding to the Royal Marsden and Institute of Cancer Research Biomedical Research Centre.
J. Hornberger: Employee: Genomic Health. R.P. Graf: Employee: Epic Sciences. G. Attard: Honoraria: Astellas Pharma; Janssen; Consulting, Advisory role: Abbott Laboratories, Astellas Pharma, Bayer, ESSA, Janssen-Cilag, Medivation, Millennium, Novartis, Ventana Medical Systems; Veridex Speakers' bureau: Astellas Pharma, Janssen, Sanofi, Takeda, Ventana Medical Systems; Research funding: Arno Therapeutics (Inst), Innocrin Pharma (Inst), Janssen (Inst), Patents, Royalties: Other intellectual property: The ICR rewards to inventors list of abiraterone acetate; Travel, accommodations, expenses: Abbott Laboratories, Astellas Pharma, Astellas Pharma (I), Bayer, ESSA, Janssen, Janssen (I), Medivation, Ventana Medical Systems. R. Dittamore: Employee: Epic Sciences. H.I. Scher: Consultant: Sanofi (C), Clovis (C), Janssen (U), Pfizer (U); Grant/Research support: MSK, Innocrin, Janssen; Board of Directors: Asterias, Biotherapeutics; Advisory board: WCG Oncology (C). All other authors have declared no conflicts of interest.