The EMBARK trial demonstrated that enzalutamide ± leuprolide significantly improved metastasis-free survival (MFS) in patients with nonmetastatic castration-sensitive prostate cancer with high-risk biochemical recurrence (hrBCR). This post hoc analysis reports the efficacy and safety results when patients were stratified by age.
The EMBARK trial (NCT02319837) included patients with hrBCR after local therapy, prostate-specific antigen (PSA) doubling time ≤ 9 months, and PSA ≥ 2 ng/mL above nadir post radiotherapy (RT) or ≥ 1 ng/mL after radical prostatectomy ± postoperative RT. Patients were randomized (1:1:1) to enzalutamide with leuprolide (combination), leuprolide and placebo (leuprolide alone), or enzalutamide alone (monotherapy). This analysis compares MFS and safety outcomes by age group (<70 vs ≥70 years).
Of 1068 patients, 543 (51 %) were aged < 70 years and 525 (49 %) were aged ≥ 70 years. Patients ≥ 70 years had higher median baseline PSA and higher rates of primary RT versus patients < 70 years across all treatment groups. Improvements in MFS were observed in the combination and monotherapy groups compared with leuprolide alone, regardless of age. Treatment-related serious adverse events (TRSAEs) and grade ≥ 3 AEs were more common in patients aged ≥ 70 years versus < 70 years for all treatment groups, but TRSAEs were low in all treatment and age groups (TRSAEs: 0.6-11.7 %; grade ≥3 AEs: 36.3-60.1 %).
Clinically meaningful improvements in MFS were observed following enzalutamide ± leuprolide in patients with hrBCR regardless of age. TRSAEs were more common in older patients but were low regardless of age. These findings should be interpreted in light of small subgroup sizes.
European journal of cancer (Oxford, England : 1990). 2025 Nov 15 [Epub ahead of print]
Neal D Shore, Ugo De Giorgi, Matko Kalac, Yiyun Tang, Ruslan Croitoru, Matt Rosales, Melissa J Huynh, Igle J de Jong, Christopher P Evans, Flavio M Carcano, Stephen J Freedland
START Carolinas/Carolina Urologic Research Center, Myrtle Beach, SC, USA., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy., Global Product Development, Pfizer Inc, New York, NY, USA., Global Product Development, Pfizer Inc, South San Francisco, CA, USA., Global Product Development, Astellas Pharma Inc, Northbrook, IL, USA., Western University, Department of Surgery, London Health Sciences Centre, Victoria Hospital, London, ON, Canada., University Medical Centrum Groningen, Department Urologie, Groningen, Netherlands., University of Nevada, Reno School of Medicine, Reno, NV, USA., Oncoclínicas & Co - Medica Scientia Innovation Research (MEDSIR), Sao Paulo, Brazil; Barretos Cancer Hospital, Barretos, Brazil., Department of Urology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Durham VA Medical Center, Durham, NC, USA. Electronic address: .