Introduction:

Relugolix is a first-in-class, oral, highly selective, GnRH receptor antagonist approved in the United States for the treatment of men with advanced prostate cancer. In the phase 3 HERO study, relugolix was well tolerated and demonstrated suppression of testosterone to castrate levels in 96.7% of men  at week 48, which was superior to leuprolide (89%). Here, we explore the impact of baseline testosterone (T) levels on advanced prostate cancer outcomes in the HERO study.

Methods:

The HERO study evaluated 930 men with advanced prostate cancer who underwent 2:1 randomization and received relugolix 120 mg orally once daily after a single loading dose of 360 mg or leuprolide 3-month injections for 48 weeks. Patients with baseline serum T <150 ng/dL were excluded. Subgroups analyzed for baseline T levels were <280 ng/dL or ≥280 ng/dL (cut-off based on lower limit of normal). Assessments analyzed included sustained T suppression to castrate levels (<50 ng/dL) from day 29 through 48 weeks (primary endpoint), early (day 4 and day 15) and profound (<20 ng/dL) castration rates, PSA levels, and safety. 

Results:

Of the 912 men with baseline T collected in the HERO study, 147 men (relugolix:96; leuprolide:51) had baseline T levels of <280 ng/dL and 765 patients (relugolix:516; leuprolide:249) had ≥280 ng/dL. Point estimates for sustained castration rates through 48 weeks were higher in the relugolix group versus the leuprolide group in both subgroups: <280 ng/dL (97.3% vs 84.1%) and ≥280 ng/dL. (96.5% vs 89.3%). Differences in sustained castrations rates at week 48 between relugolix and leuprolide groups were: 13.2% (95% CI: 2.4%, 24.0%) in <280 ng/dL and 7.2% (95% CI: 3.0%, 11.4%) in ≥280 ng/dL. Results for key secondary endpoints consistently favored relugolix vs leuprolide. No clinically relevant differences were noted in the incidence or types of adverse events within treatment groups in the subgroups analyzed.

Conclusion:

In this subgroup analysis, relugolix was effective with a similar safety profile regardless of baseline T levels. These results are consistent with those of the overall population in the HERO study.

Funding: Myovant Sciences GmbH, in collaboration with Pfizer, Inc.