EMBARK: enzalutamide with or without leuprolide in high-risk biochemically recurrent prostate cancer
In men whose PSA was rising fast after surgery or radiotherapy without visible metastases, enzalutamide with or without hormone injections delayed metastases by years compared with hormone injections alone, with treatment paused when the PSA fell to undetectable.
Overview
Phase 3 trial of 1,068 men with high-risk biochemical recurrence (PSA doubling time of nine months or less) after definitive therapy randomised to enzalutamide plus leuprolide, placebo plus leuprolide, or enzalutamide alone, with treatment suspended at week 37 if PSA was undetectable.
Five-year metastasis-free survival was 87.3 percent with the combination against 71.4 percent with leuprolide alone (hazard ratio 0.42) and 80.0 percent with enzalutamide monotherapy (hazard ratio 0.63); later analysis showed an overall survival benefit for the combination.
- Five-year metastasis-free survival 87.3 percent (combination) vs 71.4 percent (leuprolide alone); hazard ratio 0.42.
- Enzalutamide monotherapy 80.0 percent; hazard ratio 0.63.
Enzalutamide, with or without androgen deprivation, is now approved for high-risk biochemical recurrence, and intermittent therapy with treatment suspension is built into the regimen.
- Conventional imaging defined the population; PSMA PET would reclassify many as metastatic.
- Hot flushes, fatigue and gynaecomastia (with monotherapy) are common.