Enzalutamide (AR inhibitor) + testosterone suppression extends 8-year OS in mHSPC vs first-gen NSAAs (ENZAMET)

Enzalutamide is a potent androgen receptor (AR) signaling inhibitor, and in the ENZAMET Phase 3 trial (NCT02446405) it was added to testosterone suppression (ADT) and compared against ADT + a first-generation non-steroidal anti-androgen (NSAA; clinician’s choice; early concurrent docetaxel allowed). At 8.1-year median follow-up, enzalutamide improved OS (median 7.9 vs 5.8 years; 8-year OS 50% vs 40%; HR 0.73, 95% CI 0.63–0.86; p=0.0001) and clinical PFS at 8 years (43% vs 20%; HR 0.49, 95% CI 0.42–0.57; p<0.0001) in a broad mHSPC population (n=1125). Grade 3–5 AE rates per 100 person-years were similar for cardiac (2.2 vs 2.2) and nervous system disorders (2.3 vs 2.0), with more falls on enzalutamide (0.70 vs 0.24); non–prostate cancer deaths were similar (78 vs 76), and most patients still on enzalutamide at cutoff remained at full dose (88% at 160mg).