Treatment of mCRPC in the AR-axis-targeted therapy-resistant state

The increased use of the androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide in first- and second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) has improved patient outcomes, but resistance to these agents is inevitable.

Early identification of patients with primary or secondary resistance to ARAT therapy is of increasing clinical concern.

PubMed and conference proceedings were searched for studies of agents used after progression on abiraterone or enzalutamide. The key search terms (or aliases) used a combination of mCRPC and abiraterone or enzalutamide, and results were limited to clinical trials and comparative or validation studies.

This systematic review assembles current evidence and provides an approach to treatment using available clinical factors. Issues of patient selection, use of laboratory and clinical biomarkers to identify patients at risk of poor outcomes, and the timing and sequencing of available treatment options are addressed. Our findings reveal a lack of high-level evidence regarding predictive factors and treatment of patients with resistance to ARAT therapy, and a need for further research in this area. In the meantime, we suggest practical strategies to guide management of ARAT treatment-resistant patients based on available data.

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2015 Jun 22 [Epub ahead of print]

K Chi, S J Hotte, A M Joshua, S North, A W Wyatt, L L Collins, F Saad

Division of Medical Oncology, British Columbia Cancer Agency, Vancouver. , Department of Oncology, Juravinski Cancer Center, Hamilton. , Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto. , Department of Oncology, Cross Cancer Institute, Edmonton. , Department of Urologic Sciences, Vancouver Prostate Centre, Vancouver. , Kaleidoscope Strategic, Toronto. , Division of Urology, University of Montreal Hospital Center, Montreal, Canada