Plasma Copy Number Changes and Outcome to Abiraterone and Enzalutamide.

Plasma androgen receptor () copy number (CN) status identifies castration-resistant prostate cancer (CRPC) patients with worse outcome on abiraterone/enzalutamide. However, the impact of CN changes on clinical outcome in CRPC is unknown. Plasma samples from 73 patients treated with abiraterone or enzalutamide were collected at baseline and at the time of progression disease (PD). Droplet digital polymerase chain reaction was used to assess CN status. We showed that 11 patients (15.1%) changed CN status from baseline to PD (9 patients from normal to gain, 2 from gain to normal). Patients changing CN status from normal at baseline to gain at PD had intermediate median overall survival (OS) of 20.5 months (95% CI = 8.0-44.2) between those who remained CN normal from baseline to PD (27.3 months [95% CI = 21.9-34.4]) and those who remained CN gain from baseline to PD (9.1 months [95% CI = 3.8-14.5], < 0.0001). Patients changing CN from normal at baseline to gain at PD had a median progression-free survival (PFS) of 9.2 months (95% CI = 2.0-14.7), patients who remained CN normal had a median PFS of 9.1 months (95% CI = 7.2-10.1), and patients who remained CN gain had a median PFS of 5.4 (95% CI = 3.6-6.5, = 0.0005). Both OS and PFS were not significantly different between patients with CN that changes from normal to gain and patients with stable CN normal. We showed that CRPC patients changing CN status from baseline to progression time point had intermediate OS and we suggested that CN evaluation at baseline could be the most informative for clinical outcome of CRPC patients treated with abiraterone or enzalutamide. Larger prospective studies are warranted.