Abiraterone and enzalutamide are indicated for the treatment of patients with metastatic CRPC. However, these drugs are ineffective in some patients, and the disease progresses rapidly. Scientists used next-generation sequencing (NGS) and digital PCR to identify associations between AR gene aberrations and copy number (CN) gain detected in plasma and the outcome of abiraterone or enzalutamide treatment in CRPC. In the primary cohort, there was a significant association between AR gain and a shorter overall survival (OS) in both chemotherapy-naïve patients (median OS 12.4 months versus not reached; HR 3.98; 95% CI 1.74–9.10; P<0.001) and patients previously treated with docetaxel (median OS 9.51 versus 21.8 months; HR 3.81; P<0.001). AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel abiraterone-treated patients, and were also associated with worse OS (HR 3.26; P=0.004). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; P<0.001), radiographic-PFS (rPFS) (HR 8.06; P<0.001) and OS (HR 11.08; P=0.004). These results revealed that plasma AR gene status is an independent predictor of hormone therapy outcome in CRPC.
Conteduca V, Wetterskog D, Sharabiani MTA, et al., Ann Oncol. 2017. 0: 1–9.