Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer
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Samanta Salvi1, Valentina Casadio1, Vincenza Conteduca2, Cristian Lolli2, Giorgia Gurioli1, Filippo Martignano1,4, Giuseppe Schepisi2, Sara Testoni3, Emanuela Scarpi3, Dino Amadori2, Daniele Calistri1, Gerhardt Attard5, Ugo De Giorgi2
1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
2Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
3Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
4University of Florence, Florence, Italy
5The Institute of Cancer Research and The Royal Marsden, London, UK
Samanta Salvi, email: [email protected]
Ugo De Giorgi, email: [email protected]
Keywords: enzalutamide, androgen receptor, circulating cell free DNA, copy number variation, prostate cancer
Received: March 04, 2016 Accepted: April 27, 2016 Published: May 13, 2016
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.
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