Background: In EMBARK, enzalutamide + leuprolide and enzalutamide monotherapy showed improvements in metastasis-free survival (MFS) versus placebo + leuprolide (alone) in patients with high-risk biochemically recurrent (BCR) prostate cancer. Based on serum prostate-specific antigen (PSA) response, treatment was suspended at week 37 in 304 (85.9%) patients in the enzalutamide monotherapy arm and 240 (67.8%) in the leuprolide alone arm. Outcomes with enzalutamide monotherapy versus leuprolide alone by treatment suspension status are presented. Methods: EMBARK is a double-blind, phase 3 study of patients with high-risk BCR (PSA doubling time [PSADT] ≤9 months and PSA ≥2 ng/mL above nadir post radiotherapy or ≥1 ng/mL after radical prostatectomy [RP] ± postoperative radiotherapy). Patients were randomized (1:1) to enzalutamide monotherapy (160 mg/day, open label) or leuprolide alone (22.5 mg every 12 weeks). PSA <0.2 ng/mL at week 36 triggered treatment suspension at week 37; treatment restarted when PSA reached ≥2 ng/mL or ≥5 ng/mL for patients with or without primary RP, respectively. Proportion of patients with undetectable PSA 2 years after treatment suspension was a secondary endpoint. MFS (by blinded independent central review) was analyzed descriptively by suspension status. P-values were nominal. Results: In the suspension group, 3-year MFS rate (95% CI) was 88.1% (83.8-91.4%) for enzalutamide monotherapy and 90.0% (85.3-93.2%) for leuprolide alone; there was no clinically meaningful difference in MFS (HR 0.840, 95% CI 0.575-1.226; P=0.3659). In the no suspension group, 3-year MFS rates were 88.5% (68.5-96.2%) and 66.9% (55.4-76.1%), respectively; the number of MFS events was limited (n=4) for enzalutamide monotherapy with an observed HR (95% CI) of 0.340 (0.118-0.985). In the suspension group versus the no suspension group, a greater proportion received prior RP (enzalutamide monotherapy: 78.9 vs 41.9%; leuprolide alone: 78.3 vs 52.2%) or RP and radiotherapy (enzalutamide monotherapy: 50.7 vs 16.1%; leuprolide alone: 55.0 vs 38.0%); baseline median PSADT was similar (enzalutamide monotherapy: 4.9 vs 5.9 months; leuprolide alone: 5.0 vs 4.8 months). The proportion (95% CI) of patients with undetectable PSA 2 years after treatment suspension was 4.6% (2.5-7.6%) for enzalutamide monotherapy and 9.6% (6.2-14.0%) for leuprolide alone (P=0.0326). Conclusions: In patients with high-risk BCR who suspended treatment, the treatment effect on MFS with enzalutamide monotherapy was not different compared with leuprolide alone, though more patients reached treatment suspension criteria. In the no suspension group, enzalutamide monotherapy prolonged MFS versus leuprolide alone, though the number of MFS events was limited (n=4). Patients with prior RP were more likely to reach the PSA threshold for treatment suspension. Few patients who suspended treatment had undetectable PSA after 2 years, regardless of treatment. © 2024 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2024 Genitourinary Cancers Symposium. All rights reserved. Clinicaltrials.gov: NCT02319837. Funding: Pfizer Inc. and Astellas Pharma Inc., the co-developers of enzalutamide. Acknowledgments: Medical writing and editorial support, funded by the sponsors, were provided by Megan Christian and Rosie Henderson of Onyx (a division of Prime, London, UK).
