Fig. 1: MFS among patients with high-risk BCR treated with enzalutamide combination or monotherapy versus leuprolide alone.

A Enzalutamide combination versus leuprolide alone in the EAU-defined subpopulation^a and B Enzalutamide combination versus leuprolide alone in the protocol-defined EMBARK population; C Enzalutamide monotherapy versus leuprolide alone in the EAU-defined subpopulation^a; and D Enzalutamide monotherapy versus leuprolide alone in the protocol-defined EMBARK population. Data cutoff date: January 31, 2023. P-value was based on a stratified log-rank test and hazard ratio (with associated 95% CIs) was calculated using a stratified Cox regression model, with Kaplan–Meier method to summarize time-to-event endpoints. Stratification factors included PSA level at screening (≤ 10 ng/mL vs > 10 ng/mL), PSADT (≤ 3 mo vs > 3 mo to ≤ 9 mo), and prior hormonal therapy (yes or no) as reported in the interactive web-response system. P-values for post hoc MFS comparisons in the EAU high-risk subpopulation are nominal without adjustment for multiplicity. In the primary analysis of EMBARK, MFS (primary endpoint) improvements with enzalutamide combination versus leuprolide alone were consistent across multiple prespecified baseline characteristic subgroups, including the short-PSADT subgroups (≤ 3 mo and > 3 to ≤ 6 mo) [6]. Thus, the results in the EAU-consistent subpopulation were not adjusted for the observed imbalances in baseline characteristics, i.e., PSADT categories and pelvic soft tissue lesions, and were presented descriptively. ^aThe EAU high-risk BCR subpopulation excluded EMBARK patients with prior RT only and a GS ≤ 7. Per EMBARK protocol, all patients with prior RP had a PSADT ≤ 9 mo, regardless of their GS, and therefore met EAU criteria for post-RP high-risk BCR; patients with prior RT only and a GS > 7 (equivalent to ISUP grade 4‒5) were also considered high-risk, consistent with the EAU definition of post-RT high-risk BCR. ^bFrom The New England Journal of Medicine, Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND, Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer, 389 (16), 1453–65. Copyright © (2023) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. BCR biochemical recurrence, CI confidence interval, combination enzalutamide plus leuprolide, EAU European Association of Urology, GS Gleason score, ISUP International Society of Urological Pathologists, leuprolide alone leuprolide plus placebo, MFS metastasis-free survival, mo month, monotherapy enzalutamide monotherapy, no number, NR not reached, PSA prostate-specific antigen, PSADT PSA doubling time, RP radical prostatectomy, RT radiation therapy.