Trial design: This study is a prospective multi-center observational study among men with mCRPC designed to explore biomarkers in patients treated with radium-223. Key inclusion criteria include: (i) histologic confirmation of prostate cancer, (ii) documented criteria (PCWG2) for CRPC, (iii) availability of tumour tissue, (iv) candidacy for standard treatment with radium-223. Blood samples will be collected before, during and after progression on radium-223. The primary end point is to validate the prognostic value for overall survival (OS) of serum bone metabolism marker expression as previously described by Lara et al. . Briefly, these entities include markers for bone resorption (N-telopeptide and pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline phosphatase) . Secondary end points include (i) to analyze the prognostic role for PSA response with regard to bone metabolism marker expression (ii) to correlate radiological response with bone metabolism markers, (iii) to investigate the association of skeletal related events with bone metabolism markers, (iv) to analyze the prognostic role of alkaline phosphatase before and during radium-223, (v) to analyze the prognostic value of “Bone Scan Index” in response evaluation, (vi) to analyze the prognostic role for OS of AR-V7 and AR amplification, and (vii) to validate the prognostic role of the mRNA expression signature previously described by Olmos et al.  in peripheral blood. Exploratory outcomes will include (i) validation of prognostic nomograms described for CRPC, and (ii) exploration of new somatic and germinal variants in peripheral blood and tissue associated to response and resistance to radium-223. There will be 161 patients accrued to provide appropriate statistical power to detect at least 85 events (deaths) to analyze the primary outcome. There are currently 48 centers actively recruiting and 54 patients have been included. Clinical trial identification: NCT02925702
Speaker: Rafael Morales Barrera, Vall d’Hebron Institutde of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain
Co-Authors: M. Sáez (Malaga, Spain) N. Romero-Laorden (Madrid, Spain) R. Lozano Mejorada (Madrid, Spain) D. Lorente Estelles (Valencia, Spain) G. De Velasco (Madrid, Spain) M. Gonzalez Del Alba Baamonde (Palma de Mallorca, Spain) E. Gonzalez Billalabeitia (Murcia, Spain) A. Medina (A Coruña, Spain) P. Borrega García (Cáceres, Spain) A. Rodriguez-Vida (Barcelona, Spain) U. Fernandez Freire (Badalona, Spain) O. Fernandez Calvo (Ourense, Spain) R. García Domínguez (Salamanca, Spain) J. Puente (Madrid, Spain) J. Piulats Rodriguez (Barcelona, Spain) R. Villatoro (Málaga, Spain) E. Castro Marcos (Madrid, Spain) D. Olmos Hidalgo (Madrid, Spain)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.
2. Lara PN Jr, Ely B, Quinn DI, et al. Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421. J Natl Cancer Inst 2014;106(4):dju013.
3. Olmos D, Brewer D, Clark J, et al. Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: A prospective, two-stage study. Lancet Oncol 2012;13(11):1114-1124.