Testosterone Recovery for Relugolix Versus Leuprolide in Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study.

ABSTRACT

BACKGROUND: In the HERO study, relugolix demonstrated sustained testosterone suppression superior to that of leuprolide acetate (97% vs 89%; difference 7.9% [95% confidence interval, 4.1-12%; p < 0.001]). OBJECTIVE: To analyze testosterone recovery in a prespecified subset of men from the HERO study not indicated to continue androgen deprivation therapy. DESIGN, SETTING, AND PARTICIPANTS: Men (N = 934) were randomized (21) to receive relugolix 120 mg orally daily or leuprolide acetate injections every 12 wk for 48 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Testosterone recovery was assessed in 184 men who completed 48 wk of treatment. During the 90-d recovery period, assessments included time to testosterone recovery (>280 ng/dl; ≥80% of baseline testosterone), serum levels of prostate-specific antigen and pituitary hormones, and adverse events. RESULTS AND LIMITATIONS: The cumulative incidence rate of testosterone recovery to >280 ng/dl at 90 d following drug discontinuation was significantly higher in the relugolix cohort (n = 137) than in the leuprolide acetate cohort (n = 47; 54% vs 3.2%; nominal p = 0.002). The median time to testosterone recovery was faster following relugolix treatment than with leuprolide acetate treatment (86.0 d vs 112.0 d). Compared with leuprolide acetate, more men treated with relugolix achieved ≥80% of baseline testosterone levels (39% vs 2.1%). Men ≤65 yr and those with baseline testosterone greater than the median had a higher incident rate of testosterone recovery. Adverse events were generally similar between treatment groups. One limitation is the short testosterone recovery follow-up period. CONCLUSIONS: Oral relugolix had faster and more complete recovery of testosterone to normal levels after treatment discontinuation than leuprolide acetate in a subset of men from the HERO study. The clinical implications of a faster testosterone recovery with relugolix may be significant for men being treated with androgen deprivation therapy and influence treatment decisions. PATIENT SUMMARY: The male hormone testosterone is reduced during androgen deprivation therapy for prostate cancer. Reduced testosterone levels cause side effects, impacting patient quality of life. When treatment is stopped, the side effects lessen over time as the levels of testosterone come back to pretreatment range (testosterone recovery). In this study, we found that the time to testosterone recovery was faster with relugolix than with leuprolide acetate.