Eight-year outcomes of testosterone suppression plus enzalutamide or a non-steroidal anti-androgen for metastatic, hormone-sensitive prostate cancer (ENZAMET; ANZUP 1304)

BACKGROUND: We previously reported that, at median follow-ups of 34 and 68 months, enzalutamide improved overall survival (OS) compared with a first-generation non-steroidal anti-androgen (NSAA) when added to testosterone suppression for metastatic hormone-sensitive prostate cancer (mHSPC). We now report longer-term outcomes, with a focus on adverse events and causes of death. PATIENTS AND METHODS: Participants with mHSPC were randomly assigned (1:1) to daily enzalutamide or NSAA in addition to testosterone suppression; concurrent early docetaxel was permitted at clinician discretion. OS was the primary endpoint; secondary endpoints included progression-free survival (PFS), cause-specific survival, duration of treatment, and adverse events (AE). RESULTS: At a median follow-up of 8.1 years (97 months), deaths occurred in 285/563 (51%) participants assigned enzalutamide versus 337/562 (60%) assigned NSAA. OS was longer with enzalutamide than NSAA (median years 7.9 vs 5.8; OS at 8 years 50% vs 40%; HR 0.73, 95% CI 0.63 to 0.86; p=0.0001). Clinical PFS at 8 years also favoured enzalutamide (43% vs 20%; HR=0.49, 95% CI 0.42 to 0.57; p<0.0001). Of 622 deaths, 468 were attributed to prostate cancer and were fewer with enzalutamide than NSAA (207 vs 261), whereas deaths attributed to other causes occurred with similar frequency in the two groups (78 vs 76). Median treatment duration was 4.8 years with enzalutamide and 1.9 years with NSAA group. Of 185/563 (33%) participants still receiving enzalutamide at data-cut-off, most (163/185, 88%) remain on the full 160mg dose. Rates of grade 3-5 AEs per 100 person-years were similar between groups for cardiac (2.2 vs 2.2) and nervous system disorders (2.3 vs 2.0), with more falls observed with enzalutamide (0.70 vs 0.24). CONCLUSION: Enzalutamide continues to provide substantial long-term OS benefit at 8 years, with sustained efficacy, maintenance of full dose in most participants, and no increase in non-prostate cancer mortality. CLINICALTRIALS: gov Identifier: NCT02446405.