Enzalutamide with or without leuprolide in patients with high-risk biochemically recurrent prostate cancer: EMBARK post hoc analysis by age.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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 %). CONCLUSION: 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.