Results of the EMBARK study was published this week (10/19/23) in NEJM. It compared high risk BCR PCa treated in 3 groups: Lupron ADT alone. Enzalutamide plus ADT. And Enzalutamide monotherapy. 5 year follow up for metastasis free survival. Results below. Interesting that Enza monotherapy (No ADT) was superior to ADT and nearly as good as the combined treatment.
Details are worth looking at in the full text. Castrate resistance was much lower with combination over ADT as was PSA progression and distant metastasis rates. Enza monotherapy has significant fatigue for many, and significant side effect of gynecomastia as expected with this. (Can be managed by breast radiation or tamoxifen). I don't see where they reported castrate resistance in the monotherapy arm??
This pretty much is the end of ADT monotherapy for the SOC in high risk BCR (or beyond). Those who cannot tolerate enza should pursue the darolutamide as the preferred ARSI in my opinion. Paul/MB
nejm.org/doi/pdf/10.1056/NE...
BACKGROUND
Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus an- drogen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown.
METHODS
In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leu- prolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety.
RESULTS
A total of 1068 patients underwent randomization: 355 were assigned to the com- bination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metas- tasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metas- tasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzaluta- mide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P=0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures.
CONCLUSIONS
In patients with prostate cancer with high-risk biochemical recurrence, enzalu- tamide plus leuprolide was superior to leuprolide alone with respect to metastasis- free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.)
