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

// Samanta Salvi 1 , Valentina Casadio 1 , Vincenza Conteduca 2 , Cristian Lolli 2 , Giorgia Gurioli 1 , Filippo Martignano 1, 4 , Giuseppe Schepisi 2 , Sara Testoni 3 , Emanuela Scarpi 3 , Dino Amadori 2 , Daniele Calistri 1 , Gerhardt Attard 5 , Ugo De Giorgi 2 1 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 4 University of Florence, Florence, Italy 5 The Institute of Cancer Research and The Royal Marsden, London, UK Correspondence to: Samanta Salvi, email: samanta.salvi@irst.emr.it Ugo De Giorgi, email: ugo.degiorgi@irst.emr.it 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 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.