BACKGROUND: External beam radiotherapy (EBRT) with neoadjuvant/adjuvant androgen 
deprivation therapy (ADT) is an established treatment option to prolong survival 
for patients with intermediate- and high-risk prostate cancer (PCa). Relugolix, 
an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was evaluated 
in this clinical setting in comparison with degarelix, an injectable GnRH 
antagonist.
OBJECTIVE: To evaluate the safety and efficacy of relugolix to achieve and 
maintain castration.
DESIGN, SETTING, AND PARTICIPANTS: A phase 2 open-label study was conducted in 
103 intermediate-risk PCa patients undergoing primary EBRT and 
neoadjuvant/adjuvant ADT between June 2014 and December 2015.
INTERVENTION: Patients randomly assigned (3:2) to 24-wk treatment with either 
daily oral relugolix or 4-wk subcutaneous depot degarelix (reference control).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the rate 
of effective castration (testosterone <1.73nmol/l) in relugolix patients between 
4 and 24 wk of treatment. Secondary endpoints included rate of profound 
castration (testosterone <0.7nmol/l), prostate-specific antigen (PSA) levels, 
prostate volume, quality of life (QoL) assessed using the Aging Males' Symptoms 
scale, and the European Organization for Research and Treatment of Cancer 
(EORTC) Quality of Life (30-item EORTC core questionnaire [EORTC QLQ-C30] and 
25-item EORTC prostate cancer module [EORTC QLQ-PR25]) questionnaires, and 
safety. No formal statistical comparisons with degarelix were planned.
RESULTS AND LIMITATIONS: Castration rates during treatment were 95% and 82% with 
relugolix and 89% and 68% with degarelix for 1.73 and 0.7nmol/l thresholds, 
respectively. Median time to castration in the relugolix arm was 4 d. During 
treatment, PSA levels and prostate volumes were reduced in both groups. Three 
months after discontinuing treatment, 52% of men on relugolix and 16% on 
degarelix experienced testosterone recovery (statistical significance of 
differences not tested). Mean and median QoL scores improved following treatment 
discontinuation. The most common adverse event was hot flush (relugolix 57%; 
degarelix 61%). Lack of blinding was a potential limitation.
CONCLUSIONS: Relugolix achieved testosterone suppression to castrate levels 
within days and maintained it over 24 wk with a safety profile consistent with 
its mechanism of action.
PATIENT SUMMARY: Oral once-daily relugolix may be a novel oral alternative to 
injectable androgen deprivation therapies.