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Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer

Salvi, S; Casadio, V; Conteduca, V; Lolli, C; Gurioli, G; Martignano, F; Schepisi, G; ... De Giorgi, U; + view all (2016) Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer. Oncotarget , 7 (25) pp. 37839-37845. 10.18632/oncotarget.9341. Green open access

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Abstract

In the present study, we aimed to evaluate the association of circulating AR copy number (CN) and outcome in a cohort of patients with advanced castration-resistant prostate cancer (CRPC) treated with enzalutamide after docetaxel. Fifty-nine CRPC patients were evaluated. AR CN was analyzed with real-time and digital PCR in the serum collected at starting of treatment. Progressive disease was defined on the basis of Prostate Cancer Working Group 2 criteria. AR CN gain was found in 21 of 59 (36%) patients. Median baseline PSA, alkaline phosphatase and lactate dehydrogenase levels were higher in the AR CN gained group (p = 0.007, p = 0.003, p = 0.0009, respectively). Median PFS of patients with AR CN gain was 2.4 (95%CI: 1.9-3.2) vs. 4.0 months (95%CI: 3.0-6.5) of those with no gain (p = 0.0004). Median OS of patients with AR CN gain was 6.1 (95%CI: 3.4-8.6) vs. 14.1 months (95%CI: 8.2-20.5) of those with no gain (p = 0.0003). At multivariate analysis, PSA decline ≥ 50% and AR CN showed a significant association with PFS (p = 0.008 and p = 0.002, respectively) and OS (p = 0.009 and p = 0.001, respectively). These findings indicate that the detection of circulating AR CN gain is a promising non-invasive biomarker for outcome prediction to enzalutamide treatment in CRPC patients.

Type: Article
Title: Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.18632/oncotarget.9341
Publisher version: https://doi.org/10.18632/oncotarget.9341
Language: English
Additional information: Licensed under a Creative Commons Attribution 3.0 License (http://creativecommons.org/licenses/by/3.0/)
Keywords: androgen receptor, circulating cell free DNA, copy number variation, enzalutamide, prostate cancer, Adult, Aged, Aged, 80 and over, Alkaline Phosphatase, Biomarkers, Tumor, DNA, Disease-Free Survival, Docetaxel, Drug Resistance, Neoplasm, Gene Dosage, Humans, L-Lactate Dehydrogenase, Male, Middle Aged, Multivariate Analysis, Neoplasm Metastasis, Phenylthiohydantoin, Prostatic Neoplasms, Castration-Resistant, Receptors, Androgen, Retrospective Studies, Taxoids, Treatment Outcome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10065013
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