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Prospective assessment of AR splice variant and multi-biomarker expression on circulating tumor cells of mCRPC patients undergoing androgen receptor targeted agents: interim analysis of PRIMERA trial (NCT04188275)

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Abstract

Circulating tumor cells detection and ARV7 expression are associated with worse clinical outcomes in metastatic Castration-Resistant Prostate Cancer (mCRPC) undergoing Androgen Receptor Targeted Agents. ARFL, PSMA and PSA may help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCPRC undergoing I line ARTA therapy terminated the planned enrollment in 2020. Here, we present a pre-planned interim analysis with 18 months of median follow-up. RT-qPCR was used to determine the CTC expression of PSA, PSMA, AR and ARV7 before starting ARTA. PSA-drop, Progression-Free and Overall Survival (PFS and OS) and their correlation with CTC detection were reported. Forty-four patients were included. CTC were detected in 43.2% of patients, of whom 8.94% expressed PSA, 15.78% showed ARV7, 63.15% and 73.68% displayed ARFL and PSMA, respectively. Biochemical response was significantly improved in CTC + vs CTC− patients, with median PSA-drop of 18.5 vs 2.5 ng/ml (p = 0.03). After a median follow-up of 18 months, 50% of patients progressed. PFS was significantly longer in CTC- patients (NR vs 16 months). Eight (18.2%) patients died, a non-significant trend in terms of OS was detected in favor of CTC− patients (NR vs 29 months, p = 0.05). AR, PSA and PSMA expression in CTC + had no significant impact on PSA-drop, PFS or OS. PRIMERA-trial confirmed the CTC detection predictive importance in mCRPC patients.

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Funding

This study was sponsored under a grant from Ipsen. Ipsen had no input into the study design, analysis or interpretation of results. Ipsen reviewed this manuscript for scientific accuracy but had no input into the content.

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  1. Giulio Francolini and Mauro Loi have contributed equally to the manuscript.

Authors and Affiliations

  1. Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni 85, 50134, Florence, Italy

    Giulio Francolini, Mauro Loi, Beatrice Detti, Vanessa Di Cataldo, Luca Visani, Monica Mangoni, Icro Meattini & Lorenzo Livi

  2. Department of Biomedical, Experimental, and Clinical Sciences “Mario Serio”, University of Florence, Florence, Italy

    Lucia Pia Ciccone, Pamela Pinzani, Francesca Salvianti, Giulia Salvatore, Mariangela Sottili, Costanza Santini, Giulio Frosini, Luca Burchini, Chiara Mattioli, Andrea Gaetano Allegra, Marianna Valzano, Cecilia Cerbai, Michele Aquilano, Viola Salvestrini, Isacco Desideri, Monica Mangoni, Icro Meattini & Lorenzo Livi

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  1. Giulio Francolini
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Correspondence to Giulio Francolini.

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Francolini, G., Loi, M., Ciccone, L.P. et al. Prospective assessment of AR splice variant and multi-biomarker expression on circulating tumor cells of mCRPC patients undergoing androgen receptor targeted agents: interim analysis of PRIMERA trial (NCT04188275). Med Oncol 39, 119 (2022). https://doi.org/10.1007/s12032-022-01756-2

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