KEY TAKEAWAYS
- The phase 3 EMBARK study evaluated the efficacy and safety of enza + ADT and enza mono in pts with high-risk BCR.
- The study’s primary endpoint was metastasis-free survival.
- Enza + ADT and enza mono treatment significantly improved MFS for high-risk BCR patients compared to pbo + ADT.
In the randomized, phase 3 study, patients (pts) with high-risk biochemical recurrence (BCR) were randomized (1:1:1) to enzalutamide (enza) 160 mg/day + leuprolide acetate (LA) (double-blind), placebo (pbo) + LA (double-blind), or enza monotherapy (mono). LA 22.5 mg was given every 12 weeks. If the prostate-specific antigen (PSA) at week 36 was <0.2 ng/mL, therapy was discontinued at week 37 and resumed when PSA was ≥2 ng/mL for pts with primary radical prostatectomy (RP), and ≥5 ng/mL without RP.
The primary endpoint of metastasis-free survival was determined by blinded, independent central review (BICR) and showed significant improvement with enza + LA compared to pbo + LA. Key secondary objectives included MFS of enza mono over pbo + LA, time to PSA progression, time to antineoplastic therapy, and overall survival (OS) of enza + LA or enza mono over pbo + LA.
A total of 1068 pts were randomized into three groups: enza + LA (n=355), pbo + LA (n=358), and enza mono (n=355). After a median follow-up of 60.7 months, according to BICR, MFS for enza + LA (HR 0.42; 95% CI 0.30 −0.61; p<0.0001) and enza mono (HR 0.63; 95% CI 0.46 −0.87; p=0.0049) were more promising than pbo + LA. The study shows remarkable improvements in the risk of PSA progression (enza + LA: HR 0.07; 95% CI, 0.03 −0.14; enza mono: HR 0.33; 95% CI, 0.23 -0.49; both p<0.0001). Furthermore, the time to first use of new antineoplastic therapy was also enhanced (enza + LA: HR 0.36; 95% CI, 0.26 −0.49; enza mono: HR 0.54; 95% CI, 0.41 −0.71; both p<0.0001). The interim OS data showed promising efficacy for both enza + LA (HR 0.59; 95% CI, 0.38 −0.91; p=0.0153, did not cross interim efficacy boundary) and enza mono (HR 0.78; 95% CI, 0.52 −1.17; p=0.2304).
Fatigue and hot flashes were the most common adverse events (AEs), but no new safety signals existed.
Enza + ADT and enza mono improved MFS vs. pbo + ADT in pts with high-risk BCR. Additionally, Enza’s safety profile has remained consistent with previous clinical studies.
Source: https://www.auajournals.org/doi/10.1097/JU.0000000000003361.09
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02319837
Shore, N.D., Luz, M.D.A., Giorgi, U.D., Gleave, M., Gotto, G.T., Haas, G.P., Ramirez-Backhaus, M., Rannikko, A., Tarazi, J., Sridharan, S., Sugg, J., Tang, Y., Tutrone, R.F., Venugopal, B., Villers, A., Woo, H.H., Zohren, F., and Freedland S.J. https://doi.org/10.1097/JU.0000000000003361.09
