Eight-year outcomes of testosterone suppression plus enzalutamide or a non-steroidal anti-androgen for metastatic, hormone-sensitive prostate cancer (ENZAMET; ANZUP 1304)
In brief
Enzalutamide raises 8-year survival to 50% versus 40% with older anti-androgen
After a median 8.1-year follow-up, men with metastatic hormone-sensitive prostate cancer receiving enzalutamide plus testosterone suppression had a ten-percentage-point higher survival rate at eight years (50% vs 40%) and lived a median of two years longer than those on a first-generation non-steroidal anti-androgen. Efficacy was sustained with most patients staying on full dose, while overall serious side-effects were similar except for more falls with enzalutamide.
- Journal
- Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
- Published
- 17 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- A Y Zhang, H Thomas, S Begbie, L Cheung, K N Chi, S Chowdhury, et al.
- PMID
- 42607762
- DOI
- 10.1016/j.annonc.2026.07.412
Why clinicians should know about it
- Picked for Urology (top studies of the week, 23 August 2026): Eight‑year ENZAMET trial shows OS benefit in mHSPC
- Picked for Oncology and Radiation Oncology (paper of the day, 18 August 2026): Eight‑year OS benefit of enzalutamide in mHSPC
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.